Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model

• Published in: PloS one Vol. 7; no. 3; p. e33633
• Main Authors: Chakraborty, Goutam, Kumar, Santosh, Mishra, Rosalin, Patil, Tushar V., Kundu, Gopal C.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2012; Public Library of Science (PLoS)
• Subjects: Ailanthus excelsa; Analysis; Angiogenesis; Animal models; Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis - drug effects; Axon sprouting; Biology; Blotting, Western; Breast cancer; Cancer; Cancer metastasis; Cancer prevention; Cancer treatment; Case-Control Studies; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Curcumin; Curcumin - pharmacology; Dacarbazine; Dacarbazine - pharmacology; Genes; Growth; Health aspects; House mouse; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Immunoenzyme Techniques; In vivo methods and tests; Inhibition; Invasiveness; Liver Neoplasms - metabolism; Liver Neoplasms - prevention & control; Liver Neoplasms - secondary; Lung Neoplasms - metabolism; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Male; Medicine; Melanoma; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - prevention & control; Phosphatase; Phosphorylation; Phosphorylation - drug effects; Prostate cancer; Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Semaphorin-3A - genetics; Semaphorin-3A - metabolism; Tumor suppressor genes; Tumorigenesis; Tumors; Vascular endothelial growth factor; Wound Healing - drug effects; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033633

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. 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. Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.