title: Hyperglycemia of tumor microenvironment modulates stage-dependent tumor progression and multidrug resistance: implication of cell survival regulatory molecules and altered glucose transport.
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.
authors.affiliation: School of Biotechnology, Banaras Hindu University, Varanasi, 221 005, UP, India.
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Vishvakarma
authors.forename: Anjani
authors.initials: A
authors.lastname: Kumar
authors.forename: Vivek
authors.initials: V
authors.lastname: Singh
authors.forename: Sukh Mahendra
authors.initials: SM
authors.lastname: Singh
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D059016:Tumor Microenvironment
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016207:Cytokines; D051272:Glucose Transporter Type 1; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495678:Slc2a1 protein, mouse; D005947:Glucose; D002945:Cisplatin