Abstract

BASIGIN/CD147/EMMPRIN is a multifunctional transmembrane glycoprotein strongly expressed in tumours. BASIGIN controls tumour metabolism, particularly glycolysis by facilitating lactic acid export through the two monocarboxylate transporters MCT1 and hypoxia-inducible MCT4. However, before being recognized as a co-carrier of MCTs, BASIGIN was described as an inducer of extracellular matrix metalloproteases (MMPs). Early on, a model emerged in which, tumour cells use the extracellular domain of BASIGIN to recognize and stimulate neighbouring fibroblasts to produce MMPs. However, this model has remained hypothetical since a direct link between BASIGIN and MMPs production has not yet been clearly established. To validate the BASIGIN/MMP hypothesis, we developed BASIGIN knockouts in three human tumour cell lines derived from glioma, colon, and lung adenocarcinoma. By using co-culture experiments of either human or mouse fibroblasts and tumour cell lines we showed, contrary to what has been abundantly published, that the disruption of BASIGIN in tumour cells and in MEFs has no action on the production of MMPs. Our findings do not support the notion that the pro-tumoural action of BASIGIN is mediated via induction of MMPs. Therefore, we propose that to date, the strongest pro-tumoural action of BASIGIN is mediated through the control of fermentative glycolysis.

Highlights

  • BASIGIN/CD147 (BSG) is a highly glycosylated transmembrane protein belonging to the immunoglobulins (Ig) super family

  • In 1982, Biswas et al [17] showed for the first time that fibroblasts co-cultured with tumour cells, or treated by tumour cell conditioned media, produced an increased collagenase activity via a soluble factor present in tumour conditioned media

  • They showed that this factor named tumour cell-derived collagenase stimulatory factor (TCSF) is present both as a soluble form and a tumour cell membrane component

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Summary

Introduction

BASIGIN/CD147 (BSG) is a highly glycosylated transmembrane protein belonging to the immunoglobulins (Ig) super family. Before being recognized as a chaperone of MCTs, BASIGIN (alternatively named EMMPRIN for Extracellular Matrix MetalloPRotease INducer) was reported to increase tumour growth and metastasis via its capacity to induce the expression of extra cellular matrix metalloproteases (MMPs) and to modify the tumour microenvironment [17,18,19]. This invasive capacity was associated with the HIF1-mediated induction of VEGF and its receptor VEGFR2 [20,21,22]. The notion that BASIGIN could serve as an inducer of MMPs is an attractive and interesting hypothesis in the context of tumour microenvironment and metastasis

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