The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

Abstract

Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment.

Up‐regulated basigin‐2 in microglia induced by hypoxia promotes retinal angiogenesis

“…While predominantly recognized for its role in multiple biological processes, such as immune response, tumour progression, matrix proteolysis and cell migration, it has also been shown to be involved especially in neovasculogenesis under hypoxia during tumour invasion and metastasis 10. Especially, it has been reported that basigin may promote angiogenic process not only through its protease‐inducing function by up‐regulating matrix metalloproteinase (MMPs) secretion 11, 12, but also directly by its ability to increase soluble forms of VEGF and VEGFR2 in tumour cells and endothelial cells 13, 14, 15.…”

“…tumour invasion and metastasis [10]. Especially, it has been reported that basigin may promote angiogenic process not only through its protease-inducing function by up-regulating matrix metalloproteinase (MMPs) secretion [11,12], but also directly by its ability to increase soluble forms of VEGF and VEGFR2 in tumour cells and endothelial cells [13][14][15].…”

CD147‐mediated glucose metabolic regulation contributes to the predictive role of 18F‐FDG PET/CT imaging for EGFR‐TKI treatment sensitivity in NSCLC

“…The majority of human tumors exhibit significantly higher glucose flux than adjacent normal tissues . Moreover, glucose metabolism in tumors is characterized by increased aerobic glycolysis, even in the presence of sufficient oxygen . The crucial roles of numerous oncogenic signals mediated by some well‐known oncoproteins and tumor suppressor proteins in metabolic reprogramming have been revealed, including the PI3K/Akt/mTOR, Myc, and hypoxia‐inducible factor pathways, which mediate increases in glucose uptake and glycolysis.…”

“…42 Moreover, glucose metabolism in tumors is characterized by increased aerobic glycolysis, even in the presence of sufficient oxygen. 43 The crucial roles of numerous oncogenic signals mediated by some well-known oncoproteins and tumor suppressor proteins in metabolic reprogramming have been revealed, 44,45 including the PI3K/Akt/mTOR, 46,47 Myc, 48 60 and irreversible small-molecule inhibitors ( 18 F-afatinib) 61 .…”

Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

“…Taken together, these data suggested that CD147 was able to mediate drug resistance in breast cancer cells though interacting with V-ATPase. CD147 has also been demonstrated to specifically be associated with cell surface expression and the appropriate location of MCTs as a chaperone in the energy metabolism of tumors, thus contributing to the tumor invasion, metastasis and drug resistance (24,(47)(48)(49). In addition, CD147 have been observed to influence tumor drug resistance through different mechanisms.…”