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Published in:

01-02-2012 | Focussed Research Review

MicroRNA regulation in cancer-associated fibroblasts

Authors: Olga Aprelikova, Jeffrey E. Green

Published in: Cancer Immunology, Immunotherapy | Issue 2/2012

Abstract

The microenvironment of cancer cells has proven to be a critical component of tumors that strongly influences cancer development and progression into invasive and metastatic disease. Compared to normal tissue, dramatic differences in gene expression occur in multiple cell types that constitute the tumor microenvironment including cancer-associated fibroblasts (CAFs) that are important stromal components of growing tumors. In this review, we present recent advances in understanding how microRNAs are deregulated in cancer-associated fibroblasts (CAFs) and how this affects tumor biology. The microRNA signature of CAFs is discussed with respect to their functional relevance to tumor cells as well as other cell types involved in tumor homeostasis.

Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1:46–54PubMedCrossRef

Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6:392–401PubMedCrossRef

Polyak K, Haviv I, Campbell IG (2009) Co-evolution of tumor cells and their microenvironment. Trends Genet 25:30–38PubMedCrossRef

Barkan D, El Touny LH, Michalowski AM, Smith JA, Chu I, Davis AS, Webster JD, Hoover S, Simpson RM, Gauldie J, Green JE (2010) Metastatic growth from dormant cells induced by a col-I-enriched fibrotic environment. Cancer Res 70:5706–5716PubMedCrossRef

Barkan D, Kleinman H, Simmons JL, Asmussen H, Kamaraju AK, Hoenorhoff MJ, Liu ZY, Costes SV, Cho EH, Lockett S, Khanna C, Chambers AF, Green JE (2008) Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res 68:6241–6250PubMedCrossRef

Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7:834–846PubMedCrossRef

Rubin H (2008) Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy? Adv Cancer Res 100:159–202PubMedCrossRef

Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, Weinberg RA (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348PubMedCrossRef

Polyak K (2007) Breast cancer: origins and evolution. J Clin Invest 117:3155–3163PubMedCrossRef

10.

Tlsty TD, Coussens LM (2006) Tumor stroma and regulation of cancer development. Annu Rev Pathol 1:119–150PubMedCrossRef

11.

Radisky DC, Kenny PA, Bissell MJ (2007) Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 101:830–839PubMedCrossRef

12.

Adegboyega PA, Mifflin RC, DiMari JF, Saada JI, Powell DW (2002) Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps, and adenomatous colorectal polyps. Arch Pathol Lab Med 126:829–836PubMed

13.

De Wever O, Mareel M (2003) Role of tissue stroma in cancer cell invasion. J Pathol 200:429–447PubMedCrossRef

14.

Begley LA, Kasina S, MacDonald J, Macoska JA (2008) The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy. Cytokine 43:194–199PubMedCrossRef

15.

Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL (2004) TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303:848–851PubMedCrossRef

16.

Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong JL, Naidu S, Wei G, Sharma SM, Stephens JA, Fernandez SA, Gurcan MN, Weinstein MB, Barsky SH, Yee L, Rosol TJ, Stromberg PC, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC, Leone G (2009) Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 461:1084–1091PubMedCrossRef

17.

Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K (2004) Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 6:17–32PubMedCrossRef

18.

Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002–5011PubMed

19.

Pietras K, Pahler J, Bergers G, Hanahan D (2008) Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 5:e19PubMedCrossRef

20.

Cardone A, Tolino A, Zarcone R, Borruto Caracciolo G, Tartaglia E (1997) Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer. Panminerva Med 39:174–177PubMed

21.

Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, Kowalski LP, Coletta RD (2008) Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol 44:509–517PubMedCrossRef

22.

Desmouliere A, Guyot C, Gabbiani G (2004) The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol 48:509–517PubMedCrossRef

23.

Micke P, Ostman A (2004) Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer 45(Suppl 2):S163–S175PubMedCrossRef

24.

Sugimoto H, Mundel TM, Kieran MW, Kalluri R (2006) Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 5:1640–1646PubMedCrossRef

25.

Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64:8492–8495PubMedCrossRef

26.

Ishii G, Sangai T, Oda T, Aoyagi Y, Hasebe T, Kanomata N, Endoh Y, Okumura C, Okuhara Y, Magae J, Emura M, Ochiya T, Ochiai A (2003) Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun 309:232–240PubMedCrossRef

27.

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–563PubMedCrossRef

28.

Rosenthal E, McCrory A, Talbert M, Young G, Murphy-Ullrich J, Gladson C (2004) Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts. Mol Carcinog 40:116–121PubMedCrossRef

29.

San Francisco IF, DeWolf WC, Peehl DM, Olumi AF (2004) Expression of transforming growth factor-beta 1 and growth in soft agar differentiate prostate carcinoma-associated fibroblasts from normal prostate fibroblasts. Int J Cancer 112:213–218PubMedCrossRef

30.

Shimoda M, Mellody KT, Orimo A (2010) Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression. Semin Cell Dev Biol 21:19–25PubMedCrossRef

31.

Erez N, Truitt M, Olson P, Arron ST, Hanahan D (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 17:135–147PubMedCrossRef

32.

Fukino K, Shen L, Matsumoto S, Morrison CD, Mutter GL, Eng C (2004) Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets. Cancer Res 64:7231–7236PubMedCrossRef

33.

Hill R, Song Y, Cardiff RD, Van Dyke T (2005) Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123:1001–1011PubMedCrossRef

34.

Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C (2002) Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 32:355–357PubMedCrossRef

35.

Moinfar F, Man YG, Arnould L, Bratthauer GL, Ratschek M, Tavassoli FA (2000) Concurrent and independent genetic alterations in the stromal and epithelial cells of mammary carcinoma: implications for tumorigenesis. Cancer Res 60:2562–2566PubMed

36.

Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88–91PubMedCrossRef

37.

Qiu W, Hu M, Sridhar A, Opeskin K, Fox S, Shipitsin M, Trivett M, Thompson ER, Ramakrishna M, Gorringe KL, Polyak K, Haviv I, Campbell IG (2008) No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas. Nat Genet 40:650–655PubMedCrossRef

38.

Walter K, Omura N, Hong SM, Griffith M, Goggins M (2008) Pancreatic cancer associated fibroblasts display normal allelotypes. Cancer Biol Ther 7:882–888PubMedCrossRef

39.

Fiegl H, Millinger S, Goebel G, Muller-Holzner E, Marth C, Laird PW, Widschwendter M (2006) Breast cancer DNA methylation profiles in cancer cells and tumor stroma: association with HER-2/neu status in primary breast cancer. Cancer Res 66:29–33PubMedCrossRef

40.

Hu M, Yao J, Cai L, Bachman KE, van den Brule F, Velculescu V, Polyak K (2005) Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 37:899–905PubMedCrossRef

41.

Jiang L, Gonda TA, Gamble MV, Salas M, Seshan V, Tu S, Twaddell WS, Hegyi P, Lazar G, Steele I, Varro A, Wang TC, Tycko B (2008) Global hypomethylation of genomic DNA in cancer-associated myofibroblasts. Cancer Res 68:9900–9908PubMedCrossRef

42.

Munker R, Calin GA (2011) MicroRNA profiling in cancer. Clin Sci (Lond) 121:141–158CrossRef

43.

Ambros V (2001) MicroRNAs: tiny regulators with great potential. Cell 107:823–826PubMedCrossRef

44.

Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedCrossRef

45.

Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452PubMedCrossRef

46.

Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM (2010) Exosomes: Fit to deliver small RNA. Commun Integr Biol 3:447–450PubMedCrossRef

47.

Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J (2010) The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9:4387–4398PubMedCrossRef

48.

Dobreva G, Dambacher J, Grosschedl R (2003) SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. Genes Dev 17:3048–3061PubMedCrossRef

49.

Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137:1032–1046PubMedCrossRef

50.

Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothe F, Simion A, Akl H, Mourtada M, El Rifai M, Burny A, Romero P, Martiat P, Badran B (2009) Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol 39:1608–1618PubMedCrossRef

51.

Hanoun N, Delpu Y, Suriawinata AA, Bournet B, Bureau C, Selves J, Tsongalis GJ, Dufresne M, Buscail L, Cordelier P, Torrisani J (2010) The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem 56:1107–1118PubMedCrossRef

52.

Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M (2008) A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 105:13556–13561PubMedCrossRef

53.

Budhu A, Jia HL, Forgues M, Liu CG, Goldstein D, Lam A, Zanetti KA, Ye QH, Qin LX, Croce CM, Tang ZY, Wang XW (2008) Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 47:897–907PubMedCrossRef

54.

Olson P, Lu J, Zhang H, Shai A, Chun MG, Wang Y, Libutti SK, Nakakura EK, Golub TR, Hanahan D (2009) MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev 23:2152–2165PubMedCrossRef

55.

Liu X, Zhan Z, Xu L, Ma F, Li D, Guo Z, Li N, Cao X (2010) MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIalpha. J Immunol 185:7244–7251PubMedCrossRef

56.

Lopez T, Hanahan D (2002) Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis. Cancer Cell 1:339–353PubMedCrossRef

57.

Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39:493–506PubMedCrossRef

58.

Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486PubMedCrossRef

59.

Musumeci M, Coppola V, Addario A, Patrizii M, Maugeri-Sacca M, Memeo L, Colarossi C, Francescangeli F, Biffoni M, Collura D, Giacobbe A, D’Urso L, Falchi M, Venneri MA, Muto G, De Maria R, Bonci D (2011) Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 30:4231–4242PubMedCrossRef

Title: MicroRNA regulation in cancer-associated fibroblasts
Authors: Olga Aprelikova
Jeffrey E. Green
Publication date: 01-02-2012
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 2/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1139-7

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