The anticancer potential of thrombospondin-1 by inhibiting angiogenesis and stroma reaction during cervical carcinogenesis

Publication date: Available online 26 September 2015 Source:Gynecology and Minimally Invasive Therapy Author(s): Ming-Ping Wu, Li-Wha Wu, Cheng-Yang Chou Tumor growth is angiogenesis dependent. Angiogenic switch (the acquisition of an angiogenic phenotype) is essential for cervical carcinogenesis. Thrombospondin-1 (TSP-1) is an endogenous angiogenic inhibitor with multiple functional domains and interacting receptors. The disruption of TSP-1 fence (the expression in basal epithelia) occurred concordantly during the transition from low-grade squamous intraepithelial lesion into high-grade squamous intraepithelial lesion. This concordance suggests that TSP-1 plays a role in the regulation of angiogenic switch during cervical carcinogenesis. Tumor vasculature as a therapeutic target offers a paradigm shift for anticancer therapy. Endothelial cells do not appear to acquire resistance during antiangiogenic therapy. Low-and-frequent dose “metronic” chemotherapy is found to be antiangiogenic, which is more effective in targeting tumor endothelia than traditional large, single bolus doses. Meanwhile, the invasion process of cancers is associated with stroma reaction, which is characterized by fibroblasts' activation. In addition to the well-known angiogenesis inhibitor, TSP-1 also has a novel role of blocking activated fibroblasts (myofibroblasts) from invading cancer. Activated fibroblasts during stroma reaction could be used as an efficient drug delivery system to pre...
Source: Gynecology and Minimally Invasive Therapy - Category: OBGYN Source Type: research