Role of disialogangliosides in proliferation and induced cell death of melanocytes and melanomas in vitro

Author(s)

Andreia Hanada Otake

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2006-03-09

Examining board members

Roger Chammas; Jose Alexandre Marzagao Barbuto; Gil Benard; Rogerio Izar Neves; Shigueko Sonohara Troyano Pueyo

• Advisor: Roger Chammas

Abstract

Disialoganglioside GD3 and its derivatives are melanoma progression markers. To evaluate the possible roles of these molecules along melanoma progression, we have transfected the GD3 synthase gene (ST8Sia I) in a melanocyte cell line. Accumulation of GD3 did not confer any proliferative advantage to melanocytes. However, GD3 expression was associated with cell survival. The autonomic growth of melanomas is in part related to a constitutive activation of fibroblast growth factor dependent pathways. GD3 expression did not alter the proliferative response to either FGF-1 or FGF-2. However, GD3 and other membrane glycospingolipids modulate the motogenic activity of FGF-2. GD3 expression sensitizes melanocytes to chemotherapeutic agent-induced cell death, as cisplatin and vimblastin. On the other hand, GD3 turned melanocytes more resistant to temozolomide. Chemosensitization to vimblastin, but not to the other drugs, was dependent on the presence of GD3 within the cells, as shown by metabolic depletion of glycosphingolipids (AU)

• FAPESP's process: 04/01695-3 - Role of disialogangliosides in proliferation and induced cell death of melanocytes and melanomas in vitro and in vivo
• Grantee: Andréia Hanada Otake
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)