کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2116836 | 1546701 | 2007 | 10 صفحه PDF | دانلود رایگان |
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 μM) abrogated the PDGF-induced DNA synthesis, and furthermore counteracted an inhibitory effect of PDGF on the expression of α-smooth muscle actin (α-SMA). High-dose imatinib mesylate (10 μM) decreased the viability of CAFs in vitro independent from co-stimulation with PDGF. Interestingly, imatinib mesylate (10 μM) 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.
Journal: Cancer Letters - Volume 250, Issue 2, 8 June 2007, Pages 329–338