Abstract
BackgroundRecent 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 FindingsIn 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.ConclusionsOur 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.
Highlights
Melanoma or malignancies of melanocytic tissues have been identified as one of the most malignant cancer in the United States and around the world
Our results demonstrate, at least in part, the functional approach underlying semaphorin 3A (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
The results revealed that significant expression of Sema 3A was observed in normal skin biopsy specimens (Fig. 1A, panel f–j)
Summary
Melanoma or malignancies of melanocytic tissues have been identified as one of the most malignant cancer in the United States and around the world. Malignant progression of cancer cells depends on intrinsic crosstalk between several factors, overexpression of various oncogenic molecules and loss of function of tumor suppressor genes. Understanding the mechanisms of various tumor suppressor genes in regulation of cancer progression and their possible role in cancer therapeutics is under intense investigation. The role of semaphorins in various physiological as well as pathophysiological processes including cell migration, regulation of immune response, angiogenesis and cancer have recently been studied [4]. Semaphorin 3A (Sema 3A), another member of this family is shown to inhibit angiogenesis and acts as tumor suppressor [13,14,15,16]. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. The function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation
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