CD147 Impacts Angiogenesis and Metastasis Formation

Abstract

CD147 is highly expressed on many tumor cells; its role for tumor invasiveness and metastasis has been deduced from its capacity to induce MMPs, i.e., MMP-1, -2, -3, and -9. However, in the murine B16 melanoma model, MMP-2/-9 expression occurs independent of CD147. To scrutinize the impact of CD147 on metastasis formation and angiogenesis in this model, CD147 was stably knocked down in B16 cells. This silencing of CD147 expression resulted in a reduced capability of the tumor cells to metastasize to the draining lymph nodes. Notably, the CD147 knock down caused a decreased VEGF expression in vivo accompanied by reduced blood vessel formation. Thus, in the B16 melanoma model, CD147 promotes metastasis formation by induction of angiogenesis in an MMP independent manner.

CD147 induces up-regulation of vascular endothelial growth factor in U937-derived foam cells through PI3K/AKT pathway

“…VEGF, a pro-angiogenic growth factor, has been found correlated closely with neovessels within atherosclerotic plaques, macrophage accumulation, and plaque instability. 7,9,10 CD147, also called Extracellular Matrix Metalloproteinase Inducer(EMMPRIN), which was originally discovered on the surface of solid tumor cells, has been found the ability to promote the angiogenesis in many pathological conditions such as cancer diseases and rheumatoid arthritis via the up-regulation of VEGF [11][12][13] .Since CD147 is also discovered to play a pivotal role in the complex processes of atherogenesis and acute plaque rupture and thrombosis [14][15][16][17] , we hypothesis that CD147 would also induce the up-regulation of VEGF in foam cells formation in atherosclerosis.…”

Up-regulated EMMPRIN/CD147 protein expression might play a role in colorectal carcinogenesis and its subsequent progression without an alteration of its glycosylation and mRNA level

“…Proteolysis of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is one of the most critical steps in various stages of tumor progression, including growth, invasion and metastasis of malignancies. Although many investigators have focused on the association between MMPs and aggressive cancer behaviors, the search for MMP-inducing factors in tumor cells led to the identification of EMM-PRIN, whose name reflects its Extracellular Matrix Metalloproteinase Inducer activity (Ueda et al 2005;Voigt et al 2009).…”

“…The encoded protein is a glycosylated cell surface transmembrane protein that belongs to the immunoglobin super-family. It is composed of a 185 amino acid (aa) extracellular region, a single 22 aa residue transmembrane domain, and a short 39 aa residue cytoplasmic domain (Voigt et al 2009;Gabison et al 2005b;Nabeshima et al 2006). The extracellular region contains three N-linked glycosylation sites, associated with 5-35 kDa glycosylation content, which is responsible for the MMP-stimulating activity.…”

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

“…MMP-9, which is a member of the MMP family, is involved in breakdown of the extracellular matrix (ECM), which promotes tumor invasion and metastasis. CD147 is a highly glycosylated transmembrane protein that regulates many protein families and that affects tumor invasiveness and metastasis [12,36,37]. MMP-9 and CD147 expression is associated with the malignant potential of pancreatic cancer cells [38], NSCLC cells [12] bladder cancer cells [13] and breast cancer cells [39].…”