Possibilities for Treatment of Melanoma: Effects on Cell Proliferation by Inhibition of Melanoma Chondroitin Sulfate Proteoglycan (MCSP) and B‐Raf In Vitro

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Possibilities for Treatment of Melanoma: Effects on Cell Proliferation by Inhibition of Melanoma Chondroitin Sulfate Proteoglycan (MCSP) and B‐Raf In Vitro

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2010-04-21

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The Map-Kinase cell signaling pathway controls cell growth by allowing cells to divide only in the presence of growth factor. Amplification of extracellular signaling proteins to downstream cytoplasmic signaling proteins B-RAF, Mek and Erk 1,2 leads to transcription of proteins involved in cell-cycle control. In 60% of Melanomas, B-RAF is found in a mutated form allowing division even in the absence of growth factors. Additionally, Melanoma Chondroitin Sulfate Proteoglycan is absent in normal melanocytes while frequently expressed in melanomas. MCSP sustains constitutive activation of Erk 1,2. Thus, it is of clinical significance to consider MCSP and B-RAF as cellular candidates for treatment of Melanoma due their modulation of Erk1, 2 activation. To determine cell proliferation effects by inhibition of MCSP and B-RAF, melanoma cell lines A375 and WM1341D were used. A375 contains MCSP and does not have mutant BRAF while WM1341D shows expression of MCSP and mutant B-RAF. Cells were treated with Raf kinase inhibitor Bay 43-9006 against B-RAF and MCSP antibody against MCSP. Simultaneous treatment had additive effects on A375 cell line while synchronous drug addition in WM1341D was not as effective as single administration of either MCSP antibody or Bay 43-9006. Thus, there was sensitization of A375 to Bay 43-9006 treatment by the addition of antibody while WM1341D cells showed resistance by the addition of antibody to Bay 43-9006.

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Additional contributors: Jianbo Yang; Kaoru Terai; Soldano Ferrone; Xinhui Wang; James B. McCarthy; Arkadiusz Z. Dudek (faculty mentor).

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Cespedes Gomez, Omar. (2010). Possibilities for Treatment of Melanoma: Effects on Cell Proliferation by Inhibition of Melanoma Chondroitin Sulfate Proteoglycan (MCSP) and B‐Raf In Vitro. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/61804.

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