CD147 immunoglobulin superfamily receptor function and role in pathology

Abstract

The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to upregulation of CD147 expression and tumor progression is introduced.

Figure 1. The CD147-MCT complex promotes tumor progression

A.) Under hypoxic conditions within the tumor microenvironment rapid tumor proliferation is achieved by anaerobic glycolysis, the byproduct of which is lactic acid. Coordinate upregulation of hypoxia inducible factor, HIF-1α, results in increased transcription of MCT (Moeller et al. 2005; Moeller et al. 2006) and increased cell surface expression of the CD147-MCT complex after their assembly in the Golgi apparatus. Tumor viability is maintained by the MCT facilitated transport of lactic acid into the peritumoral space thus regulating intracellular pH. B) Peritumoral cytotoxic T cell (Tc) function is inhibited by increased lactic acid in the tumor microenvironment (Fischer et al. 2007) enabling unchecked tumor growth. Increased CD147 expression induces MMP production by neighboring fibroblasts (Kataoka et al. 1993; Biswas et al. 1995; Guo et al. 1997; Sun et al. 2001) resulting in breakdown of the extracellular matrix and metastasis of CD147 expressing tumor cells.