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Endothelin‐1 stimulates colon cancer adjacent fibroblasts
Author(s) -
Knowles Jonathan P.,
ShiWen Xu,
Haque Samerul,
Bhalla Ashish,
Dashwood Michael R.,
Yang Shiyu,
Taylor Irving,
Winslet Marc C.,
Abraham David J.,
Loizidou Marilena
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26090
Subject(s) - stroma , biology , extracellular matrix , cancer research , fibroblast , downregulation and upregulation , microbiology and biotechnology , in vitro , immunology , gene , immunohistochemistry , biochemistry
Endothelin‐1 (ET‐1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET‐1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET‐1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET‐1 stimulated proliferation, contraction and migration ( p < 0.01 v control) and the expression of matrix degrading enzymes TIMP‐1 and MMP‐2, but not MMP‐3. ET‐1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET‐1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET‐1 is proposed as a target for adjuvant cancer therapy.