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Endothelin-1 stimulates colon cancer adjacent fibroblasts.

Knowles, JP; Shi-Wen, X; Haque, S-U; Bhalla, A; Dashwood, MR; Yang, S; Taylor, I; ... Loizidou, M; + view all (2012) Endothelin-1 stimulates colon cancer adjacent fibroblasts. Int J Cancer , 130 (6) pp. 1264-1272. 10.1002/ijc.26090.

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Abstract

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.

Type: Article
Title: Endothelin-1 stimulates colon cancer adjacent fibroblasts.
Location: United States
DOI: 10.1002/ijc.26090
Keywords: Actins, Cell Growth Processes, Cell Movement, Colonic Neoplasms, Endothelin-1, Extracellular Matrix, Fibroblasts, Humans, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 2, Receptor, Endothelin A, Receptor, Endothelin B, Receptors, Growth Factor, Tissue Inhibitor of Metalloproteinase-1, Tumor Cells, Cultured, Up-Regulation
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: http://discovery.ucl.ac.uk/id/eprint/1301542
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