Chondroitin sulfate proteoglycan-4 does not protect melanoma cells during inhibition of PI3K and mTOR pathways.

Abstract

BACKGROUND:

Chondroitin sulfate proteoglycan-4 (CSPG4) is commonly expressed in melanoma cells and induces melanoma cell proliferation and migration by enhancement of activation of the extracellular signal-regulated kinase 1, 2 (ERK1,2) pathway. The phosphoinositide 3-kinase (PI3K) -protein kinase B (AKT) and mammalian target of rapamycin (mTOR) pathways are also frequently de-regulated in melanoma. We hypothesized that CSPG4, by sustained activation of PI3K, may reduce the effect of the dual inhibition of PI3K-AKT and mTOR pathways.

MATERIALS AND METHODS:

CSPG4-negative melanoma cell line WM1552C was transfected with CSPG4 and CSPG4 lacking cytoplasmic domain (melanoma-associated chondroitin sulfate proteoglycan (MCSP)ΔCD). To assess the effect of CSPG4 on the mTOR pathway, PF-5212384, a dual PI3K/mTOR inhibitor was used. Cell proliferation and downstream signaling from mTOR was assayed in the presence of CSPG4.

RESULTS:

Forced CSPG4 expression did not provide any protection to melanoma cells from the pharmacological inhibition of mTOR pathway in vitro. In addition, we demonstrated that inhibition of signaling molecules downstream of AKT and mTOR was not diminished in the presence of CSPG4 when the cells were treated with the PI3K/mTOR inhibitor.

CONCLUSION:

CSPG4 expression does not have any impact on survival and signaling activity of melanoma cells during PI3K/mTOR inhibition.

• Authors: Sehrish Javaid, Kaoru Terai, Arkadiusz Z Dudek
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 3 Pg. 1279-84 (Mar 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25750275 (Publication Type: Journal Article)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antigens
• Phosphoinositide-3 Kinase Inhibitors
• Proteoglycans
• chondroitin sulfate proteoglycan 4
• MTOR protein, human
• TOR Serine-Threonine Kinases

Topics

• Antigens (physiology)
• Cell Line, Tumor
• Cell Proliferation
• Humans
• Melanoma (pathology)
• Phosphoinositide-3 Kinase Inhibitors
• Proteoglycans (physiology)
• Signal Transduction (physiology)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)