Hyperglycemia of tumor microenvironment modulates stage-dependent tumor progression and multidrug resistance: implication of cell survival regulatory molecules and altered glucose transport

Molecular Carcinogenesis
Naveen Kumar VishvakarmaSukh Mahendra Singh

Abstract

Using a murine tumor model, we demonstrate that tumor cells display a tumor stage-dependent differential glucose utilization associated with an altered GLUT-1 expression. Hyperglycemic tumor microenvironment modulates the tumorigenic ability, survival, apoptosis, and glucose utilization of tumor cells in late tumor-bearing stage accompanied by an altered tumor acidosis and expression of cell survival regulatory molecules: HIF-1α, p53, Bcl2, caspase-activated DNase, IL-4, IL-6, IL-10, IFN-γ, TGF-β, and VEGF. Glucose-exposed tumor cells of late tumor-bearing stage also show a declined susceptibility to the cytotoxic action of chemotherapeutic drugs: cisplatin and methotrexate, accompanied by an increased expression of MDR-1 gene. Taken together the results show that hyperglycemic tumor microenvironment differentially alters tumor growth depending on the stage of tumor progression.

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Citations

Nov 3, 2015·Expert Review of Anticancer Therapy·Maria MoschoviSpiros Vlahopoulos
Mar 4, 2014·Journal of Vascular and Interventional Radiology : JVIR·Mehran Midia
Jan 13, 2018·Journal of Bioenergetics and Biomembranes·Andréia Vasconcelos-Dos-SantosWagner B Dias
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Oct 26, 2021·Frontiers in Oncology·Vivek Kumar SoniNaveen Kumar Vishvakarma

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