semaphorin 3a suppresses tumor growth and metastasis in mice melanoma model3 semaphorin抑制小鼠黑色素瘤模型中肿瘤的生长和转移.pdfVIP

Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model 1¤ 1. 1. 2 1 Goutam Chakraborty , Santosh Kumar , Rosalin Mishra , Tushar V. Patil , Gopal C. Kundu * 1 National Center for Cell Science (NCCS), NCCS Complex, Pune, India, 2 Department of Histopathology, YCM Hospital, Pune, India Abstract Background: Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation. Methodology/Principal Findings: In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents. Conclusions: Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a cl