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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Impact of PINCH expression on survival in colorectal cancer patients

Authors: Jasmine Lööf, Johan Rosell, Charlotte Bratthäll, Siv Doré, Hans Starkhammar, Hong Zhang, Xiao-Feng Sun

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer.

Results

Paraffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% CI, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% CI, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen.

Conclusions

PINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.
Appendix
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Literature
1.
Rearden A: A new LIM protein containing an autoepitope homologous to "senescent cell antigen". Biochemical and biophysical research communications. 1994, 201 (3): 1124-1131. 10.1006/bbrc.1994.1822.CrossRefPubMed
2.
Dawid IB, Breen JJ, Toyama R: LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet. 1998, 14 (4): 156-162. 10.1016/S0168-9525(98)01424-3.CrossRefPubMed
3.
Hobert O, Moerman DG, Clark KA, Beckerle MC, Ruvkun G: A conserved LIM protein that affects muscular adherens junction integrity and mechanosensory function in Caenorhabditis elegans. J Cell Biol. 1999, 144 (1): 45-57. 10.1083/jcb.144.1.45.CrossRefPubMedPubMedCentral
4.
Tu Y, Li F, Goicoechea S, Wu C: The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. Mol Cell Biol. 1999, 19 (3): 2425-2434.CrossRefPubMedPubMedCentral
5.
Tu Y, Li F, Wu C: Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways. Mol Biol Cell. 1998, 9 (12): 3367-3382.CrossRefPubMedPubMedCentral
6.
Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, et al: Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature. 1996, 379 (6560): 91-96. 10.1038/379091a0.CrossRefPubMed
7.
Wang-Rodriguez J, Dreilinger AD, Alsharabi GM, Rearden A: The signaling adapter protein PINCH is up-regulated in the stroma of common cancers, notably at invasive edges. Cancer. 2002, 95 (6): 1387-1395. 10.1002/cncr.10878.CrossRefPubMed
8.
Gao J, Arbman G, Rearden A, Sun XF: Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. Neoplasia. 2004, 6 (6): 796-801. 10.1593/neo.04304.CrossRefPubMedPubMedCentral
9.
Zhang JT, Li QX, Wang D, et al: Up-regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis. Oncol Rep. 2005, 14 (6): 1519-1522.PubMed
10.
Purdie CA, Piris J: Histopathological grade, mucinous differentiation and DNA ploidy in relation to prognosis in colorectal carcinoma. Histopathology. 2000, 36 (2): 121-126. 10.1111/j.1365-2559.2000.00826.x.CrossRefPubMed
11.
Li H, Fan X, Houghton J: Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem. 2007, 101 (4): 805-815. 10.1002/jcb.21159.CrossRefPubMed
12.
De Wever O, Mareel M: Role of tissue stroma in cancer cell invasion. J Pathol. 2003, 200 (4): 429-447. 10.1002/path.1398.CrossRefPubMed
13.
Fukuda T, Chen K, Shi X, Wu C: PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J Biol Chem. 2003, 278 (51): 51324-51333. 10.1074/jbc.M309122200.CrossRefPubMed
14.
Berrier AL, Yamada KM: Cell-matrix adhesion. J Cell Physiol. 2007, 213 (3): 565-573. 10.1002/jcp.21237.CrossRefPubMed
15.
16.
Chiarugi P, Giannoni E: Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol. 2008, 76 (11): 1352-1364. 10.1016/j.bcp.2008.07.023.CrossRefPubMed
17.
Li Y, Dai C, Wu C, Liu Y: PINCH-1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. J Am Soc Nephrol. 2007, 18 (9): 2534-2543. 10.1681/ASN.2007030315.CrossRefPubMed
18.
Thiery JP: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 2003, 15 (6): 740-746. 10.1016/j.ceb.2003.10.006.CrossRefPubMed
19.
Tsushima H, Kawata S, Tamura S, et al: High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology. 1996, 110 (2): 375-382. 10.1053/gast.1996.v110.pm8566583.CrossRefPubMed
20.
Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S: Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc Natl Acad Sci USA. 1998, 95 (19): 11211-11216. 10.1073/pnas.95.19.11211.CrossRefPubMedPubMedCentral
21.
Takanami I: Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer. BMC Cancer. 2005, 5: 1-10.1186/1471-2407-5-1.CrossRefPubMedPubMedCentral
22.
Marotta A, Tan C, Gray V, et al: Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis. Oncogene. 2001, 20 (43): 6250-6257. 10.1038/sj.onc.1204791.CrossRefPubMed
23.
Dai DL, Makretsov N, Campos EI, et al: Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival. Clin Cancer Res. 2003, 9 (12): 4409-4414.PubMed
24.
Wu C, Keightley SY, Leung-Hagesteijn C, et al: Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity. J Biol Chem. 1998, 273 (1): 528-536. 10.1074/jbc.273.1.528.CrossRefPubMed
25.
Radeva G, Petrocelli T, Behrend E, et al: Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression. J Biol Chem. 1997, 272 (21): 13937-13944. 10.1074/jbc.272.21.13937.CrossRefPubMed
26.
Koshida Y, Kuranami M, Watanabe M: Interaction between stromal fibroblasts and colorectal cancer cells in the expression of vascular endothelial growth factor. J Surg Res. 2006, 134 (2): 270-277. 10.1016/j.jss.2006.02.025.CrossRefPubMed
27.
Singer CF, Kronsteiner N, Marton E, et al: MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions. Breast Cancer Res Treat. 2002, 72 (1): 69-77. 10.1023/A:1014918512569.CrossRefPubMed
28.
Tan C, Cruet-Hennequart S, Troussard A, et al: Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell. 2004, 5 (1): 79-90. 10.1016/S1535-6108(03)00281-2.CrossRefPubMed
29.
Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971, 285 (21): 1182-1186. 10.1056/NEJM197111182852108.CrossRefPubMed
30.
Dassoulas K, Gazouli M, Theodoropoulos G, et al: Vascular endothelial growth factor and endoglin expression in colorectal cancer. J Cancer Res Clin Oncol. 2009
31.
32.
Kitadai Y, Haruma K, Tokutomi T, et al: Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas. Clin Cancer Res. 1998, 4 (9): 2195-2200.PubMed
33.
Du JR, Jiang Y, Zhang YM, Fu H: Vascular endothelial growth factor and microvascular density in esophageal and gastric carcinomas. World J Gastroenterol. 2003, 9 (7): 1604-1606.CrossRefPubMedPubMedCentral
34.
Maeda K, Chung YS, Ogawa Y, et al: Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996, 77 (5): 858-863. 10.1002/(SICI)1097-0142(19960301)77:5<858::AID-CNCR8>3.0.CO;2-A.CrossRefPubMed
35.
Troussard AA, Costello P, Yoganathan TN, Kumagai S, Roskelley CD, Dedhar S: The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9). Oncogene. 2000, 19 (48): 5444-5452. 10.1038/sj.onc.1203928.CrossRefPubMed
36.
Woessner JF: Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991, 5 (8): 2145-2154.PubMed
37.
Westermarck J, Kahari VM: Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999, 13 (8): 781-792.PubMed
38.
Sato T, Sakai T, Noguchi Y, Takita M, Hirakawa S, Ito A: Tumor-stromal cell contact promotes invasion of human uterine cervical carcinoma cells by augmenting the expression and activation of stromal matrix metalloproteinases. Gynecol Oncol. 2004, 92 (1): 47-56. 10.1016/j.ygyno.2003.09.012.CrossRefPubMed
39.
Di Nezza LA, Misajon A, Zhang J, et al: Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer. 2002, 94 (5): 1466-1475. 10.1002/cncr.10355.CrossRefPubMed
40.
Kurahara S, Shinohara M, Ikebe T, et al: Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck. 1999, 21 (7): 627-638. 10.1002/(SICI)1097-0347(199910)21:7<627::AID-HED7>3.0.CO;2-2.CrossRefPubMed
41.
Jones JL, Glynn P, Walker RA: Expression of MMP-2 and MMP-9, their inhibitors, and the activator MT1-MMP in primary breast carcinomas. J Pathol. 1999, 189 (2): 161-168. 10.1002/(SICI)1096-9896(199910)189:2<161::AID-PATH406>3.0.CO;2-2.CrossRefPubMed
42.
Nagase H, Visse R, Murphy G: Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006, 69 (3): 562-573. 10.1016/j.cardiores.2005.12.002.CrossRefPubMed
43.
Aglund K, Rauvala M, Puistola U, et al: Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage. Gynecol Oncol. 2004, 94 (3): 699-704. 10.1016/j.ygyno.2004.06.028.CrossRefPubMed
44.
Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T: Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis. Clin Cancer Res. 2004, 10 (9): 3110-3116. 10.1158/1078-0432.CCR-03-0530.CrossRefPubMed
45.
Theret N, Musso O, Turlin B, et al: Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Hepatology. 2001, 34 (1): 82-88. 10.1053/jhep.2001.25758.CrossRefPubMed
46.
Kaspar M, Zardi L, Neri D: Fibronectin as target for tumor therapy. Int J Cancer. 2006, 118 (6): 1331-1339. 10.1002/ijc.21677.CrossRefPubMed
47.
Danen EH, Yamada KM: Fibronectin, integrins, and growth control. J Cell Physiol. 2001, 189 (1): 1-13. 10.1002/jcp.1137.CrossRefPubMed
48.
Miyamoto S, Katz BZ, Lafrenie RM, Yamada KM: Fibronectin and integrins in cell adhesion, signaling, and morphogenesis. Ann N Y Acad Sci. 1998, 857: 119-129. 10.1111/j.1749-6632.1998.tb10112.x.CrossRefPubMed
49.
Ioachim E, Charchanti A, Briasoulis E, et al: Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer. 2002, 38 (18): 2362-2370. 10.1016/S0959-8049(02)00210-1.CrossRefPubMed
50.
Das S, Banerji A, Frei E, Chatterjee A: Rapid expression and activation of MMP-2 and MMP-9 upon exposure of human breast cancer cells (MCF-7) to fibronectin in serum free medium. Life Sci. 2008, 82 (9-10): 467-476. 10.1016/j.lfs.2007.12.013.CrossRefPubMed
51.
Maity G, Fahreen S, Banerji A, et al: Fibronectin-integrin mediated signaling in human cervical cancer cells (SiHa). Mol Cell Biochem. 2009
52.
Bhardwaj B, Klassen J, Cossette N, et al: Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res. 1996, 2 (4): 773-782.PubMed
53.
Kitadai Y, Sasaki T, Kuwai T, et al: Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential. Int J Cancer. 2006, 119 (11): 2567-2574. 10.1002/ijc.22229.CrossRefPubMed
54.
Klintrup K, Makinen JM, Kauppila S, et al: Inflammation and prognosis in colorectal cancer. Eur J Cancer. 2005, 41 (17): 2645-2654. 10.1016/j.ejca.2005.07.017.CrossRefPubMed
Metadata
Title
Impact of PINCH expression on survival in colorectal cancer patients
Authors
Jasmine Lööf
Johan Rosell
Charlotte Bratthäll
Siv Doré
Hans Starkhammar
Hong Zhang
Xiao-Feng Sun
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-103

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