Melanoma is one of the deadliest tumors. Despite the advances in understanding the
melanoma cell biology and drug discoveries, treatment resistance remains a challenge.
Chondroitin sulfate proteoglycan (CSPG4) is expressed on the surface of melanoma
cells, and its role in metastatic progression has been established. One known mechanism
responsible for this activity is modulation of the activity of ERK1,2. PI3k/mTOR
pathway is also frequently deregulated in melanomas . We therefore investigated if
CSPG4 has an impact on PI3K/mTOR pathway activity. Our results indicate that
CSPG4 causes resistance to growth inhibition and apoptosis in early stage melanoma
cell lines. The knockdown of CSPG4 sensitized the advanced disease stage cell lines to
growth inhibition. CSPG4 also induced resistance at various levels of mTOR pathway
in different cell lines, and resulted in inhibition of motility and invasion in response to
treatment with PF-05212384, a potent PI3K/mTOR inhibitor. Melanoma cell lines
derived from all stages of melanoma growth showed resistance to inhibition of 4ebp1.
Our results indicate that CSPG4 play a role in decreased sensitivity of melanoma cells
to mTOR pathway inhibition.
University of Minnesota M.S. thesis. July 2012. Major: Oral Biology. Advisor: Arkadiusz Dudek. 1 computer file (PDF); vi, 40 pages.
Investigation of the role of chondroitin sulfate proteoglycan in causing treatment resistance in melanoma to PI3k/mTOR inhibition..
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