Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics

1.

Adjei IM, Blanka S (2015) Modulation of the tumor microenvironment for cancer treatment: a biomaterials approach. J Functional biomater 6:81–103. doi:10.3390/jfb6010081 CrossRef

2.

Alvarez R, Musteanu M, Garcia-Garcia E, Lopez-Casas PP, Megias D, Guerra C, Munoz M, Quijano Y, Cubillo A, Rodriguez-Pascual J, Plaza C, de Vicente E, Prados S, Tabernero S, Barbacid M, Lopez-Rios F, Hidalgo M (2013) Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br J Cancer 109:926–933. doi:10.1038/bjc.2013.415 PubMedCentralPubMedCrossRef

3.

Angelo M, Bendall SC, Finck R, Hale MB, Hitzman C, Borowsky AD, Levenson RM, Lowe JB, Liu SD, Zhao S, Natkunam Y, Nolan GP (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20:436–442. doi:10.1038/nm.3488 PubMedCentralPubMedCrossRef

4.

Ariga N, Sato E, Ohuchi N, Nagura H, Ohtani H (2001) Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast. Int J Cancer J Int du Cancer 95:67–72CrossRef

5.

Barth RF, Coderre JA, Vicente MGH, Blue TE (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002. doi:10.1158/1078-0432.Ccr-05-0035 PubMedCrossRef

6.

Bello IO, Vered M, Dayan D, Dobriyan A, Yahalom R, Alanen K, Nieminen P, Kantola S, Laara E, Salo T (2011) Cancer-associated fibroblasts, a parameter of the tumor microenvironment, overcomes carcinoma-associated parameters in the prognosis of patients with mobile tongue cancer. Oral Oncol 47:33–38. doi:10.1016/j.oraloncology.2010.10.013 PubMedCrossRef

7.

Benoit DSW, Schwartz MP, Durney AR, Anseth KS (2008) Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater 7:816–823. doi:10.1038/Nmat2269 PubMedCentralPubMedCrossRef

8.

Bersani F, Lee J, Yu M, Morris R, Desai R, Ramaswamy S, Toner M, Haber DA, Parekkadan B (2014) Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res 74:7229–7238. doi:10.1158/0008-5472.CAN-14-1809 PubMedPubMedCentralCrossRef

9.

Bersani F, Lee J, Yu M, Morris R, Desai R, Ramaswamy S, Toner M, Haber DA, Parekkadan B (2014) Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res. doi:10.1158/0008-5472.CAN-14-1809 PubMedPubMedCentral

10.

Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32:760–772. doi:10.1038/nbt.2989 PubMedCrossRef

11.

Bracher M, Bezuidenhout D, Lutolf MP, Franz T, Sun M, Zilla P, Davies NH (2013) Cell specific ingrowth hydrogels. Biomaterials 34:6797–6803. doi:10.1016/j.biomaterials.2013.05.057 PubMedCrossRef

12.

Brennen WN, Rosen DM, Wang H, Isaacs JT, Denmeade SR (2012) Targeting carcinoma-associated fibroblasts within the tumor stroma with a fibroblast activation protein-activated prodrug. J Natl Cancer I 104:1320–1334. doi:10.1093/Jnci/Djs336 CrossRef

13.

Bueno L, de Alwis DP, Pitou C, Yingling J, Lahn M, Glatt S, Troconiz IF (2008) Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-beta kinase antagonist, in mice. Eur J Cancer 44:142–150. doi:10.1016/j.ejca.2007.10.008 PubMedCrossRef

14.

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, Sevillano M, Palomo-Ponce S, Tauriello DV, Byrom D, Cortina C, Morral C, Barcelo C, Tosi S, Riera A, Attolini CS, Rossell D, Sancho E, Batlle E (2015) Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 47:320–329. doi:10.1038/ng.3225 PubMedCrossRef

15.

Castello-Cros R, Cukierman E (2009) Stromagenesis during tumorigenesis: characterization of tumor-associated fibroblasts and stroma-derived 3D matrices. Methods Mol Biol 522:275–305. doi:10.1007/978-1-59745-413-1_19 PubMedCentralPubMedCrossRef

16.

Chen Y, Zou L, Zhang Y, Chen Y, Xing P, Yang W, Li F, Ji X, Liu F, Lu X (2014) Transforming growth factor-beta1 and alpha-smooth muscle actin in stromal fibroblasts are associated with a poor prognosis in patients with clinical stage I-IIIA nonsmall cell lung cancer after curative resection. Tumour Biol J Int Soc Oncodev Biol Med 35:6707–6713. doi:10.1007/s13277-014-1908-y CrossRef

17.

Cohen SJ, Alpaugh RK, Palazzo I, Meropol NJ, Rogatko A, Xu Z, Hoffman JP, Weiner LM, Cheng JD (2008) Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas 37:154–158. doi:10.1097/MPA.0b013e31816618ce PubMedCrossRef

18.

de Kruijf EM, van Nes JG, van de Velde CJ, Putter H, Smit VT, Liefers GJ, Kuppen PJ, Tollenaar RA, Mesker WE (2011) Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res Treat 125:687–696. doi:10.1007/s10549-010-0855-6 PubMedCrossRef

19.

De Sousa EMF, Wang X, Jansen M, Fessler E, Trinh A, de Rooij LP, de Jong JH, de Boer OJ, van Leersum R, Bijlsma MF, Rodermond H, van der Heijden M, van Noesel CJ, Tuynman JB, Dekker E, Markowetz F, Medema JP, Vermeulen L (2013) Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 19:614–618. doi:10.1038/nm.3174 CrossRef

20.

De Vlieghere E, Gremonprez F, Verset L, Mariën L, Christopher JJ, De Craene B, Berx G, Descamps B, Vanhove C, Remon J, Ceelen W, Demetter P, Bracke M, De Geest B, De Wever O (2015) Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells. Biomaterials 54:148–157. doi:10.1016/j.biomaterials.2015.03.012 PubMedCrossRef

21.

De Wever O, Demetter P, Mareel M, Bracke M (2008) Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer J Int du Cancer 123:2229–2238. doi:10.1002/ijc.23925 CrossRef

22.

De Wever O, Hendrix A, De Boeck A, Eertmans F, Westbroek W, Braems G, Bracke ME (2014) Single cell and spheroid collagen type I invasion assay. Methods Mol Biol 1070:13–35. doi:10.1007/978-1-4614-8244-4_2 PubMedCrossRef

23.

De Wever O, Mareel M (2002) Role of myofibroblasts at the invasion front. Biol Chem 383:55–67. doi:10.1515/BC.2002.006 PubMedCrossRef

24.

De Wever O, Van Bockstal M, Mareel M, Hendrix A, Bracke M (2014) Carcinoma-associated fibroblasts provide operational flexibility in metastasis. Semin Cancer Biol 25:33–46. doi:10.1016/j.semcancer.2013.12.009 PubMedCrossRef

25.

Dekker TJ, van de Velde CJ, van Pelt GW, Kroep JR, Julien JP, Smit VT, Tollenaar RA, Mesker WE (2013) Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854). Breast Cancer Res Treat 139:371–379. doi:10.1007/s10549-013-2571-5 PubMedCrossRef

26.

Denys H, Derycke L, Hendrix A, Westbroek W, Gheldof A, Narine K, Pauwels P, Gespach C, Bracke M, De Wever O (2008) Differential impact of TGF-beta and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion. Cancer Lett 266:263–274. doi:10.1016/j.canlet.2008.02.068 PubMedCrossRef

27.

Ding L, Zhang Z, Shang D, Cheng J, Yuan H, Wu Y, Song X, Jiang H (2014) Alpha-smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma. J of Oral Pathol Med Off Publ Int Assoc Oral Pathologists Am Acad Oral Pathol 43:335–343. doi:10.1111/jop.12143 CrossRef

28.

Duluc C, Moatassim-Billah S, Chalabi-Dchar M, Perraud A, Samain R, Breibach F, Gayral M, Cordelier P, Delisle MB, Bousquet-Dubouch MP, Tomasini R, Schmid H, Mathonnet M, Pyronnet S, Martineau Y, Bousquet C (2015) Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumour chemoresistance. EMBO Mol Med. doi:10.15252/emmm.201404346 PubMedCentralPubMed

29.

Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659. doi:10.1056/NEJM198612253152606 PubMedCrossRef

30.

Fujii N, Shomori K, Shiomi T, Nakabayashi M, Takeda C, Ryoke K, Ito H (2012) Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. J Oral Pathol Med Off Publ Int Assoc Oral Pathologists Am Acad Oral Pathol 41:444–451. doi:10.1111/j.1600-0714.2012.01127.x CrossRef

31.

Gao W, Xiang B, Meng TT, Liu F, Qi XR (2013) Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides. Biomaterials 34:4137–4149. doi:10.1016/j.biomaterials.2013.02.014 PubMedCrossRef

32.

Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37:1590–1598. doi:10.1016/S0959-8049(01)00171-X PubMedCrossRef

33.

Ghajar CM, Bissell MJ (2010) Tumor engineering: the other face of tissue engineering. Tissue engineering. Part A 16:2153–2156. doi:10.1089/ten.TEA.2010.0135

34.

Grimminger F, Gunther A, Vancheri C (2015) The role of tyrosine kinases in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J. doi:10.1183/09031936.00149614

35.

Ha SY, Yeo SY, Xuan YH, Kim SH (2014) The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma. PLoS One 9:e99955. doi:10.1371/journal.pone.0099955 PubMedCentralPubMedCrossRef

36.

Hartman O, Zhang C, Adams EL, Farach-Carson MC, Petrelli NJ, Chase BD, Rabolt JE (2010) Biofunctionalization of electrospun PCL-based scaffolds with perlecan domain IV peptide to create a 3-D pharmacokinetic cancer model. Biomaterials 31:5700–5718. doi:10.1016/j.biomaterials.2010.03.017 PubMedCentralPubMedCrossRef

37.

Hartman O, Zhang C, Adams EL, Farach-Carson MC, Petrelli NJ, Chase BD, Rabolt JF (2009) Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications. Biomacromolecules 10:2019–2032. doi:10.1021/Bm8012764 PubMedCentralPubMedCrossRef

38.

Health NIo ClinicalTrials.gov. https://clinicaltrials.gov/

39.

Henry LR, Lee HO, Lee JS, Klein-Szanto A, Watts P, Ross EA, Chen WT, Cheng JD (2007) Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res Off J Am Assoc Cancer Res 13:1736–1741. doi:10.1158/1078-0432.CCR-06-1746 CrossRef

40.

Herrera M, Herrera A, Dominguez G, Silva J, Garcia V, Garcia JM, Gomez I, Soldevilla B, Munoz C, Provencio M, Campos-Martin Y, Garcia de Herreros A, Casal I, Bonilla F, Pena C (2013) Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci 104:437–444. doi:10.1111/cas.12096 PubMedCrossRef

41.

Herrera M, Islam AB, Herrera A, Martin P, Garcia V, Silva J, Garcia JM, Salas C, Casal I, de Herreros AG, Bonilla F, Pena C (2013) Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature. Clin Cancer Res Off J Am Assoc Cancer Res 19:5914–5926. doi:10.1158/1078-0432.CCR-13-0694 CrossRef

42.

Herrmann D, Conway JR, Vennin C, Magenau A, Hughes WE, Morton JP, Timpson P (2014) Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment. Carcinogenesis 35:1671–1679. doi:10.1093/carcin/bgu108 PubMedCrossRef

43.

Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ (2008) BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 68:4774–4782. doi:10.1158/0008-5472.CAN-07-6307 PubMedCrossRef

44.

Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, De Wever O, Mareel M, Gabbiani G (2012) Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 180:1340–1355. doi:10.1016/j.ajpath.2012.02.004 PubMedCentralPubMedCrossRef

45.

Huang TQ, Qu X, Liu J, Chen SC (2014) 3D printing of biomimetic microstructures for cancer cell migration. Biomed Microdevices 16:127–132. doi: 10.1007/s10544-013-9812-6

46.

Huijbers A, Tollenaar RA, Pelt GW v, Zeestraten EC, Dutton S, CC MC, Domingo E, Smit VT, Midgley R, Warren BF, Johnstone EC, Kerr DJ, Mesker WE (2013) The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol Off J Eur Soc Med Oncol/ESMO 24:179–185. doi:10.1093/annonc/mds246 CrossRef

47.

Hutmacher DW, Loessner D, Rizzi S, Kaplan DL, Mooney DJ, Clements JA (2010) Can tissue engineering concepts advance tumor biology research? Trends Biotechnol 28:125–133. doi:10.1016/j.tibtech.2009.12.001 PubMedCrossRef

48.

Isella C, Terrasi A, Bellomo SE, Petti C, Galatola G, Muratore A, Mellano A, Senetta R, Cassenti A, Sonetto C, Inghirami G, Trusolino L, Fekete Z, De Ridder M, Cassoni P, Storme G, Bertotti A, Medico E (2015) Stromal contribution to the colorectal cancer transcriptome. Nat Genet 47:312–319. doi:10.1038/ng.3224 PubMedCrossRef

49.

Ito M, Ishii G, Nagai K, Maeda R, Nakano Y, Ochiai A (2012) Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma. Chest 142:151–158. doi:10.1378/chest.11-2458 PubMedCrossRef

50.

Ivkov R, DeNardo SJ, Daum W, Foreman AR, Goldstein RC, Nemkov VS, DeNardo GL (2005) Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer. Clin Cancer Res Off J Am Assoc Cancer Res 11:7093 s–7103 s. doi:10.1158/1078-0432.CCR-1004-0016 CrossRef

51.

Jeon JH, Kim SK, Kim HJ, Chang J, Ahn CM, Chang YS (2008) Insulin-like growth factor-1 attenuates cisplatin-induced gammaH2AX formation and DNA double-strand breaks repair pathway in non-small cell lung cancer. Cancer Lett 272:232–241. doi:10.1016/j.canlet.2008.07.011 PubMedCrossRef

52.

Jing J, Alaimo D, De Vlieghere E, Jerome C, De Wever O, De Geest BG, Auzely-Velty R (2013) Tunable self-assembled nanogels composed of well-defined thermoresponsive hyaluronic acid-polymer conjugates. J Mater Chem B 1:3883–3887. doi:10.1039/C3tb20283f CrossRef

53.

Kawase A, Ishii G, Nagai K, Ito T, Nagano T, Murata Y, Hishida T, Nishimura M, Yoshida J, Suzuki K, Ochiai A (2008) Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma. Int J Cancer J Int du Cancer 123:1053–1059. doi:10.1002/ijc.23611 CrossRef

54.

Kawashiri S, Tanaka A, Noguchi N, Hase T, Nakaya H, Ohara T, Kato K, Yamamoto E (2009) Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Head Neck 31:1346–1353. doi:10.1002/hed.21097 PubMedCrossRef

55.

Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, Nishimoto I, Kowalski LP, Coletta RD (2007) Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathology 51:849–853. doi:10.1111/j.1365-2559.2007.02873.x PubMedCrossRef

56.

Kenny HA, Krausz T, Yamada SD, Lengyel E (2007) Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. Int J Cancer J Int du Cancer 121:1463–1472. doi:10.1002/ijc.22874 CrossRef

57.

Kitano H, Kageyama S, Hewitt SM, Hayashi R, Doki Y, Ozaki Y, Fujino S, Takikita M, Kubo H, Fukuoka J (2010) Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival. Arch Pathol Lab Med 134:1520–1527. doi:10.1043/2009-0114-OA.1 PubMed

58.

Koriyama H, Ishii G, Yoh K, Neri S, Morise M, Umemura S, Matsumoto S, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A (2014) Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy. J Cancer Res Clin Oncol. doi:10.1007/s00432-014-1891-0 PubMed

59.

Lacouture ME, Morris JC, Lawrence DP, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Berzofsky JA, Hsu FJ, Guitart J (2015) Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor beta by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immun 64:437–446. doi: 10.1007/s00262-015-1653-0

60.

Lamagna C, Aurrand-Lions M, Imhof BA (2006) Dual role of macrophages in tumor growth and angiogenesis. J Leukoc Biol 80:705–713. doi:10.1189/jlb.1105656 PubMedCrossRef

61.

Lee H, Lee K, Park TG (2008) Hyaluronic acid-paclitaxel conjugate micelles: synthesis, characterization, and antitumor activity. Bioconjug Chem 19:1319–1325. doi:10.1021/bc8000485 PubMedCrossRef

62.

Lee J, Li M, Milwid J, Dunham J, Vinegoni C, Gorbatov R, Iwamoto Y, Wang F, Shen K, Hatfield K, Enger M, Shafiee S, McCormack E, Ebert BL, Weissleder R, Yarmush ML, Parekkadan B (2012) Implantable microenvironments to attract hematopoietic stem/cancer cells. Proc Natl Acad Sci U S A 109:19638–19643. doi:10.1073/pnas.1208384109 PubMedCentralPubMedCrossRef

63.

Lee J, Wang JB, Bersani F, Parekkadan B (2013) Capture and printing of fixed stromal cell membranes for bioactive display on PDMS surfaces. Langmuir ACS J Surf Colloid 29:10611–10616. doi:10.1021/la4012795 CrossRef

64.

Liao Y, Ni Y, He R, Liu W, Du J (2013) Clinical implications of fibroblast activation protein-alpha in non-small cell lung cancer after curative resection: a new predictor for prognosis. J Cancer Res Clin Oncol 139:1523–1528. doi:10.1007/s00432-013-1471-8 PubMedCrossRef

65.

Lotti F, Jarrar AM, Pai RK, Hitomi M, Lathia J, Mace A, Gantt Jr GA, Sukhdeo K, DeVecchio J, Vasanji A, Leahy P, Hjelmeland AB, Kalady MF, Rich JN (2013) Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J Exp med 210:2851–2872. doi:10.1084/jem.20131195

66.

Louage B, Zhang Q, Vanparijs N, Voorhaar L, Vande Casteele S, Shi Y, Hennink WE, Van Bocxlaer J, Hoogenboom R, De Geest BG (2015) Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation. Biomacromolecules 16:336–350. doi:10.1021/bm5015409 PubMedCrossRef

67.

Lybaert L, De Vlieghere E, De Rycke R, Vanparijs N, De Wever O, De Koker S, De Geest BG (2014) Bio-hybrid tumor cell-templated capsules: a generic formulation strategy for tumor associated antigens in view of immune therapy. Adv Funct Mater 24:7139–7150. doi:10.1002/adfm.201402303

68.

Marisa L, de Reynies A, Duval A, Selves J, Gaub MP, Vescovo L, Etienne-Grimaldi MC, Schiappa R, Guenot D, Ayadi M, Kirzin S, Chazal M, Flejou JF, Benchimol D, Berger A, Lagarde A, Pencreach E, Piard F, Elias D, Parc Y, Olschwang S, Milano G, Laurent-Puig P, Boige V (2013) Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 10:e1001453. doi:10.1371/journal.pmed.1001453 PubMedCentralPubMedCrossRef

69.

Marsh D, Suchak K, Moutasim KA, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette SM, Weinreb PH, Chester KA, Chana JS, Marshall JF, Hart IR, Hackshaw AK, Piper K, Thomas GJ (2011) Stromal features are predictive of disease mortality in oral cancer patients. J Pathol 223:470–481. doi:10.1002/path.2830 PubMedCrossRef

70.

Mesker WE, Junggeburt JM, Szuhai K, de Heer P, Morreau H, Tanke HJ, Tollenaar RA (2007) The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol Off J Int Soc Cell Oncol 29:387–398

71.

Miele E, Spinelli GP, Miele E, Tomao F, Tomao S (2009) Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Int J Nanomedicine 4:99–105PubMedCentralPubMed

72.

Mitra AK, Chiang CY, Tiwari P, Tomar S, Watters KM, Peter ME, Lengyel E (2015) Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis. Oncogene. doi:10.1038/onc.2015.43 PubMedCentral

73.

Moorman AM, Vink R, Heijmans HJ, van der Palen J, Kouwenhoven EA (2012) The prognostic value of tumour-stroma ratio in triple-negative breast cancer. EurJ Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 38:307–313. doi:10.1016/j.ejso.2012.01.002

74.

Morris JC, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Reiss M, Hsu FJ, Berzofsky JA, Lawrence DP (2014) Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGF beta) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. Plos One 9. doi: ARTN e90353DOI 10.1371/journal.pone.0090353

75.

Navab R, Strumpf D, Bandarchi B, Zhu CQ, Pintilie M, Ramnarine VR, Ibrahimov E, Radulovich N, Leung L, Barczyk M, Panchal D, To C, Yun JJ, Der S, Shepherd FA, Jurisica I, Tsao MS (2011) Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci U S A 108:7160–7165. doi:10.1073/pnas.1014506108 PubMedCentralPubMedCrossRef

76.

Ngan CY, Yamamoto H, Seshimo I, Tsujino T, Man-i M, Ikeda JI, Konishi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M (2007) Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer. Br J Cancer 96:986–992. doi:10.1038/sj.bjc.6603651 PubMedCentralPubMedCrossRef

77.

Ono S, Ishii G, Nagai K, Takuwa T, Yoshida J, Nishimura M, Hishida T, Aokage K, Fujii S, Ikeda N, Ochiai A (2013) Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. Chest 143:963–970. doi:10.1378/chest.12-0913 PubMedCrossRef

78.

organisation Wh. http://www.euro.who.int/en/health-topics/noncommunicable-diseases/cancer

79.

Paulsson J, Micke P (2014) Prognostic relevance of cancer-associated fibroblasts in human cancer. Semin Cancer Biol 25:61–68. doi:10.1016/j.semcancer.2014.02.006 PubMedCrossRef

80.

Popat S, Mellemgaard A, Fahrbach K, Martin A, Rizzo M, Kaiser R, Griebsch I, Reck M (2015) Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer: a network meta-analysis. Future Oncol 11:409–420. doi:10.2217/fon.14.290 PubMedCrossRef

81.

Pula B, Jethon A, Piotrowska A, Gomulkiewicz A, Owczarek T, Calik J, Wojnar A, Witkiewicz W, Rys J, Ugorski M, Dziegiel P, Podhorska-Okolow M (2011) Podoplanin expression by cancer-associated fibroblasts predicts poor outcome in invasive ductal breast carcinoma. Histopathology 59:1249–1260. doi:10.1111/j.1365-2559.2011.04060.x PubMedCrossRef

82.

Pula B, Wojnar A, Werynska B, Ambicka A, Kruczak A, Witkiewicz W, Ugorski M, Podhorska-Okolow M, Dziegiel P (2013) Impact of different tumour stroma assessment methods regarding podoplanin expression on clinical outcome in patients with invasive ductal breast carcinoma. Anticancer Res 33:1447–1455PubMed

83.

Ratajczak MZ, Jadczyk T, Schneider G, Kakar SS, Kucia M (2013) Induction of a tumor-metastasis-receptive microenvironment as an unwanted and underestimated side effect of treatment by chemotherapy or radiotherapy. J Ovarian Res 6:95. doi:10.1186/1757-2215-6-95 PubMedCentralPubMedCrossRef

84.

Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM (2011) Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 365:1079–1087. doi:10.1056/NEJMoa1103690 PubMedCrossRef

85.

Rivkin I, Cohen K, Koffler J, Melikhov D, Peer D, Margalit R (2010) Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors. Biomaterials 31:7106–7114. doi:10.1016/j.biomaterials.2010.05.067 PubMedCrossRef

86.

Rovers SA, van der Poel LAM, Dietz CHJT, Noijen JJ, Hoogenboom R, Kemmere MF, Kopinga K, Keurentjes JTF (2009) Characterization and magnetic heating of commercial superparamagnetic iron oxide nanoparticles. J Phys Chem C 113:14638–14643. doi:10.1021/Jp903333r CrossRef

87.

Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507:181–189. doi:10.1038/nature13118 PubMedCrossRef

88.

Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LC, Lannon WA, Grotzinger C, Del Rio M, Lhermitte B, Olshen AB, Wiedenmann B, Cantley LC, Gray JW, Hanahan D (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19:619–625. doi:10.1038/nm.3175 PubMedCentralPubMedCrossRef

89.

Sakai S, Liu Y, Sengoku M, Taya M (2015) Cell-selective encapsulation in hydrogel sheaths via biospecific identification and biochemical cross-linking. Biomaterials 53:494–501. doi:10.1016/j.biomaterials.2015.02.119 PubMedCrossRef

90.

Sandoval P, Jimenez-Heffernan JA, Rynne-Vidal A, Perez-Lozano ML, Gilsanz A, Ruiz-Carpio V, Reyes R, Garcia-Bordas J, Stamatakis K, Dotor J, Majano PL, Fresno M, Cabanas C, Lopez-Cabrera M (2013) Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis. J Pathol 231:517–531. doi:10.1002/path.4281 PubMedCrossRef

91.

Sawyers C (2004) Targeted cancer therapy. Nature 432:294–297. doi:10.1038/nature03095 PubMedCrossRef

92.

Schoppmann SF, Berghoff A, Dinhof C, Jakesz R, Gnant M, Dubsky P, Jesch B, Heinzl H, Birner P (2012) Podoplanin-expressing cancer-associated fibroblasts are associated with poor prognosis in invasive breast cancer. Breast Cancer Res Treat 134:237–244. doi:10.1007/s10549-012-1984-x PubMedCrossRef

93.

Schoppmann SF, Jesch B, Riegler MF, Maroske F, Schwameis K, Jomrich G, Birner P (2013) Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus. Clin Exp Metastas 30:441–446. doi: 10.1007/s10585-012-9549-2

94.

Seib FP, Berry JE, Shiozawa Y, Taichman RS, Kaplan DL (2015) Tissue engineering a surrogate niche for metastatic cancer cells. Biomaterials 51:313–319. doi:10.1016/j.biomaterials.2015.01.076 PubMedCrossRef

95.

Shindo K, Aishima S, Ohuchida K, Fujiwara K, Fujino M, Mizuuchi Y, Hattori M, Mizumoto K, Tanaka M, Oda Y (2013) Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas. Mol Cancer 12:168. doi:10.1186/1476-4598-12-168 PubMedCentralPubMedCrossRef

96.

Sinn M, Denkert C, Striefler JK, Pelzer U, Stieler JM, Bahra M, Lohneis P, Dorken B, Oettle H, Riess H, Sinn BV (2014) Alpha-smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study. Br J Cancer 111:1917–1923. doi:10.1038/bjc.2014.495 PubMedPubMedCentralCrossRef

97.

Stevenson JP, Kindler HL, Papasavvas E, Sun J, Jacobs-Small M, Hull J, Schwed D, Ranganathan A, Newick K, Heitjan DF, Langer CJ, McPherson JM, Montaner LJ, Albelda SM (2013) Immunological efects of the TGF beta-blocking antibody GC1008 in malignant pleural mesothelioma patients. Oncoimmunology 2. doi: ARTN e26218 DOI 10.4161/onci.26218

98.

Sung KE, Yang N, Pehlke C, Keely PJ, Eliceiri KW, Friedl A, Beebe DJ (2011) Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects. Integr Biol Quant Biosciences Nano Macro 3:439–450. doi:10.1039/c0ib00063a CrossRef

99.

Surowiak P, Murawa D, Materna V, Maciejczyk A, Pudelko M, Ciesla S, Breborowicz J, Murawa P, Zabel M, Dietel M, Lage H (2007) Occurence of stromal myofibroblasts in the invasive ductal breast cancer tissue is an unfavourable prognostic factor. Anticancer Res 27:2917–2924PubMed

100.

Tasso R, Augello A, Carida M, Postiglione F, Tibiletti MG, Bernasconi B, Astigiano S, Fais F, Truini M, Cancedda R, Pennesi G (2009) Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds. Carcinogenesis 30:150–157. doi:10.1093/carcin/bgn234 PubMedCrossRef

101.

Togo S, Polanska UM, Horimoto Y, Orimo A (2013) Carcinoma-associated fibroblasts are a promising therapeutic target. Cancers 5:149–169. doi:10.3390/cancers5010149 PubMedCentralPubMedCrossRef

102.

Tommelein J, Verset L, Boterberg T, Demetter P, Bracke M, De Wever O (2015) Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer. Front Oncol 5. doi:10.3389/ fonc.2015.00063

103.

Tran E, Chinnasamy D, Yu ZY, Morgan RA, Lee CCR, Restifo NP, Rosenberg SA (2013) Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J Exp Med 210:1125–1135. doi:10.1084/Jem.20130110 PubMedCentralPubMedCrossRef

104.

Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M (2007) Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res Off J Am Assoc Cancer Res 13:2082–2090. doi:10.1158/1078-0432.CCR-06-2191 CrossRef

105.

Tzouvelekis A, Bonella F, Spagnolo P (2015) Update on therapeutic management of idiopathic pulmonary fibrosis. Ther Clin Risk Manag 11:359–370. doi:10.2147/TCRM.S69716 PubMedCentralPubMed

106.

Underwood TJ, Hayden AL, Derouet M, Garcia E, Noble F, White MJ, Thirdborough S, Mead A, Clemons N, Mellone M, Uzoho C, Primrose JN, Blaydes JP, Thomas GJ (2015) Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma. J Pathol 235:466–477. doi:10.1002/path.4467 PubMedCentralPubMedCrossRef

107.

Van Bockstal M, Lambein K, Van Gele M, De Vlieghere E, Limame R, Braems G, Van den Broecke R, Cocquyt V, Denys H, Bracke M, Libbrecht L, De Wever O (2014) Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-beta1 regulates cancer cell spreading but not adhesion. Oncoscience 1:634–648PubMedCentralPubMedCrossRef

108.

van der Sanden B, Appaix F, Berger F, Selek L, Issartel JP, Wion D (2013) Translation of the ecological trap concept to glioma therapy: the cancer cell trap concept. Future Oncol 9:817–824. doi:10.2217/fon.13.30 PubMedCrossRef

109.

Vered M, Dobriyan A, Dayan D, Yahalom R, Talmi YP, Bedrin L, Barshack I, Taicher S (2010) Tumor-host histopathologic variables, stromal myofibroblasts and risk score, are significantly associated with recurrent disease in tongue cancer. Cancer Sci 101:274–280. doi:10.1111/j.1349-7006.2009.01357.x PubMedCrossRef

110.

Verset L, Tommelein J, Moles Lopez X, Decaestecker C, Boterberg T, De Vlieghere E, Salmon I, Mareel M, Bracke M, De Wever O, Demetter P (2015) Impact of neoadjuvant therapy on cancer-associated fibroblasts in rectal cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol. doi:10.1016/j.radonc.2015.05.007

111.

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703. doi:10.1056/NEJMoa1304369 CrossRef

112.

Walsh CL, Babin BM, Kasinskas RW, Foster JA, McGarry MJ, Forbes NS (2009) A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. Lab Chip 9:545–554. doi:10.1039/B810571e PubMedCentralPubMedCrossRef

113.

West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H (2010) The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 102:1519–1523. doi:10.1038/sj.bjc.6605674 PubMedCentralPubMedCrossRef

114.

Wikberg ML, Edin S, Lundberg IV, Van Guelpen B, Dahlin AM, Rutegard J, Stenling R, Oberg A, Palmqvist R (2013) High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumour Biol J Int Soc Oncodev Biol Med 34:1013–1020. doi:10.1007/s13277-012-0638-2 CrossRef

115.

Yamanashi T, Nakanishi Y, Fujii G, Akishima-Fukasawa Y, Moriya Y, Kanai Y, Watanabe M, Hirohashi S (2009) Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma. Oncology 77:53–62. doi:10.1159/000226112 PubMedCrossRef

116.

Yamashita M, Ogawa T, Zhang X, Hanamura N, Kashikura Y, Takamura M, Yoneda M, Shiraishi T (2012) Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome. Breast Cancer 19:170–176. doi:10.1007/s12282-010-0234-5 PubMedCrossRef

117.

Yao X, Choudhury AD, Yamanaka YJ, Adalsteinsson VA, Gierahn TM, Williamson CA, Lamb CR, Taplin ME, Nakabayashi M, Chabot MS, Li T, Lee GS, Boehm JS, Kantoff PW, Hahn WC, Wittrup KD, Love JC (2014) Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits. Integr Biol Quant Biosciences Nano Macro 6:388–398. doi:10.1039/c3ib40264a CrossRef

118.

Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3:1011–1022. doi:10.1038/nrd1580 PubMedCrossRef

119.

Yoshida T, Ishii G, Goto K, Neri S, Hashimoto H, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Iida S, Niimi A, Nagai K, Ohe Y, Ochiai A (2015) Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation. Clin Cancer Res Off J Am Assoc Cancer Res 21:642–651. doi:10.1158/1078-0432.CCR-14-0846 CrossRef

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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