Colorectal carcinogenesis is associated with stromal expression of COL11A1 and COL5A2.

Collagen is the major component of the interstitial extracellular matrix (ECM). ECM is known to play an active role in numerous biological processes such as cell shape, proliferation, migration, differentiation, apoptosis as well as carcinogenesis. We used mRNA differential display RT-PCR to study differentially expressed genes in tissue samples from 24 colorectal cancers and four normal colon epithelia. Twenty of the 24 tumours showed expression of a gene COL11A1, not expressed in the normal samples. This gene is not normally expressed in adult colon tissue, but was here found to be expressed in 27 out of a total of 34 (79%) colorectal carcinomas. An analysis of other collagens showed that COL5A2 was not expressed in normal colon but was co-expressed with COL11A1 in the tumours. Our results suggest that stromal expression of COL11A1 and COL5A2 is associated with malignancy in colorectal cancer.

[1]  K. Kinzler,et al.  APC mutations in colorectal tumors with mismatch repair deficiency. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Pardee,et al.  Recent advances in differential display. , 1995, Current opinion in immunology.

[3]  Peter Beighton,et al.  de la Chapelle, A. , 1997 .

[4]  Y. Collan,et al.  The distribution of collagen types I, III, and IV in normal and malignant colorectal mucosa. , 2003, The European journal of surgery = Acta chirurgica.

[5]  A. Børresen-Dale,et al.  Ki-ras mutations and prognosis in colorectal cancer. , 1998, European journal of cancer.

[6]  L. Liotta,et al.  Tumor invasion and the extracellular matrix. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[7]  K. Kinzler,et al.  Lessons from Hereditary Colorectal Cancer , 1996, Cell.

[8]  J. Nicholls,et al.  The mRNAs for the three chains of human collagen type XI are widely distributed but not necessarily co-expressed: implications for homotrimeric, heterotrimeric and heterotypic collagen molecules. , 1995, The Biochemical journal.

[9]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[10]  Scott E. Kern,et al.  Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers , 1996, Nature Genetics.

[11]  K. Tanaka,et al.  Familial polyposis: recent advances. , 1995, Critical reviews in oncology/hematology.

[12]  B. Vogelstein,et al.  p53 mutations in human cancers. , 1991, Science.

[13]  J. Willson,et al.  The type II transforming growth factor-beta receptor as a tumor-suppressor gene. , 1996, Current opinion in oncology.

[14]  Margaret Robertson,et al.  Identification and characterization of the familial adenomatous polyposis coli gene , 1991, Cell.

[15]  H. von Holst,et al.  Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion. , 1996, Brain research. Molecular brain research.

[16]  M. Schalling,et al.  The megencephaly mouse has disturbances in the insulin-like growth factor (IGF) system. , 1999, Brain research. Molecular brain research.

[17]  J. McPherson,et al.  Identification of deletion mutations and three new genes at the familial polyposis locus , 1991, Cell.

[18]  R. Béliveau,et al.  Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis. , 1999, Canadian journal of physiology and pharmacology.

[19]  J. Kleman,et al.  Another look at collagen V and XI molecules. , 1995, Matrix biology : journal of the International Society for Matrix Biology.

[20]  G. Christofori,et al.  The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. , 1999, Trends in biochemical sciences.

[21]  S. Altschul,et al.  Identification of FAP locus genes from chromosome 5q21. , 1991, Science.

[22]  Timothy J. Yeatman,et al.  Activating SRC mutation in a subset of advanced human colon cancers , 1999, Nature Genetics.

[23]  Gary R. Grotendorst,et al.  Increased content of Type V Collagen in desmoplasia of human breast carcinoma. , 1982, The American journal of pathology.

[24]  M. Karnovsky,et al.  Chronic cardiac rejection: identification of five upregulated genes in transplanted hearts by differential mRNA display. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Yoshioka,et al.  Developmental pattern of expression of the mouse α1(XI) collagen gene (Col11a1) , 1995, Developmental dynamics : an official publication of the American Association of Anatomists.

[26]  B. Marian,et al.  Skin tumor promotion is associated with increased type V collagen content in the dermis. , 1987, Carcinogenesis.

[27]  B. Spiegelman,et al.  Loss-of-Function Mutations in PPARγ Associated with Human Colon Cancer , 1999 .

[28]  M. Beckner Factors promoting tumor angiogenesis. , 1999, Cancer investigation.