Format

Send to

Choose Destination
PLoS One. 2014 Nov 17;9(11):e113103. doi: 10.1371/journal.pone.0113103. eCollection 2014.

Modeling of hypo/hyperglycemia and their impact on breast cancer progression related molecules.

Author information

1
Department of Biology, College of Science, Sultan Qaboos University, P. O. Box 36, 123 Muscat, Oman.
2
Department of Medicine, College of Medicine, Sultan Qaboos University, P.O. Box 35, 123 Muscat, Oman.
3
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.

Abstract

Breast cancer (BC) arises commonly in women with metabolic dysfunction. The underlying mechanism by which glycemic load can exert its action on tumor metastasis is under investigated. In this study we showed that glycemic microenvironment alters the expression of three classes of proteins, VEGF and its receptors, cell to cell, and cell to extracellular matrix (ECM) adhesion proteins in MDA-MB-231 parental cells and its two metastatic variants to the bone and brain (MDA-MB-231BO and MDA-MB-231BR, respectively). Using western blotting, we showed that VEGFR2 levels were higher in these variant cells and persisted in the cells under extreme hypoglycemia. Hypoglycemia did not alter VEGFR2 expression per se but rather suppressed its posttranslational glycosylation. This was reversed rapidly upon the restoration of glucose, and cyclohexamide (CHX) treatment demonstrated that this deglycosylated VEGFR2 was not a product of de-novo protein synthesis. VEGFR2 co-receptor Neuropilin-1 was up-regulated four-fold in all MDA-MB-231 cells (parental and two variants) compared to VEGFR2 expression, and was also susceptible to glycemic changes but resistant to CHX treatment for up to 72 hrs. Hypoglycemia also resulted in a significant decrease in specific catenin, cadherin, and integrin proteins, as well as cellular proliferation and colony forming ability. However, MDA-MB-231BR cells showed a unique sensitivity to hypo/hyperglycemia in terms of morphological changes, colony formation ability, integrin β3 expression and secreted VEGF levels. In conclusion, this study can be translated clinically to provide insight into breast cancer cell responses to glycemic levels relevant for our understanding of the interaction between diabetes and cancer.

PMID:
25401697
PMCID:
PMC4234670
DOI:
10.1371/journal.pone.0113103
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center