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Cancer Lett. 2007 Jun 8;250(2):329-38. Epub 2006 Dec 4.

Imatinib mesylate inhibits proliferation and modulates cytokine expression of human cancer-associated stromal fibroblasts from colorectal metastases.

Author information

1
Department of Hepatobiliary Surgery and Solid Organ Transplantation, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. l.mueller@uke.uni-hamburg.de

Abstract

Recent data have expanded the concept that cancer-associated stromal fibroblasts (CAFs) play an important role in tumor invasion and angiogenesis. Here, we show that platelet-derived growth factor (PDGF) is a mitogen for human CAFs isolated from hepatic metastases of colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate (1 microM) abrogated the PDGF-induced DNA synthesis, and furthermore counteracted an inhibitory effect of PDGF on the expression of alpha-smooth muscle actin (alpha-SMA). High-dose imatinib mesylate (10 microM) decreased the viability of CAFs in vitro independent from co-stimulation with PDGF. Interestingly, imatinib mesylate (10 microM) strikingly induced the expression of the pro-inflammatory and pro-angiogenic cytokines interleukin (IL)-6 and IL-8, and mildly stimulated the release of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Our results suggest that imatinib mesylate, due to its anti-proliferative activity, may be effective in combination with other substances for the treatment of colorectal metastasis progression.

PMID:
17141949
DOI:
10.1016/j.canlet.2006.10.024
[Indexed for MEDLINE]

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