Basigin (cd147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts

Abstract

Key words: basigin (CD147); malignant melanoma; invasion; metastasis; matrix metalloproteinaseBasigin (CD147), a transmembrane glycoprotein belonging to the Ig superfamily, was cloned from F9 embryonic carcinoma cells. 1 The Ig domain has strong homology with both the Ig variable domain and the major histocompatibility complex class II ␤ chain. It is expressed in various embryonic and adult tissues. 1,2 Because of its broad distribution, it was expected that basigin plays fundamental roles in various physiologic processes. Molecules identical to basigin were subsequently identified and given different names: M6 3 and EMMPRIN 4 in human; HT7, 5 neurothelin 6 and 5A11 7 in chicken; gp42 8 in mouse; and OX-47 9 and CE9 10 in rat. Of them, EMMPRIN, previously termed TCSF, has been implicated in the induction of MMPs. 4,11 Expression of EMMPRIN is enhanced in a variety of human carcinomas and correlates with tumor progression and invasion by inducing production of MMPs by stromal cells. 4,[11][12][13][14][15][16] It was also shown in vitro that recombinant EMMPRIN purified from Chinese hamster ovary cells transfected with cDNA for human EMMPRIN stimulates cultured human fibroblasts to produce MMP-1, MMP-2 and MMP-3. 17 EMMPRIN not only stimulates the production of interstitial collagenase (MMP-1) but also forms a complex with MMP-1 at the human lung carcinoma cell surface, which would facilitate invasive processes. 18 MMPs are a family of enzymes that degrade different components of the ECM, and a number of studies indicate that they play an important role in tissue remodeling, tumor invasion and metastasis. 19 -24 There are 2 distinct types of MMP, secreted and nonsecreted. Based on their substrate specificities, secreted MMPs are classified into collagenases (MMP-1, MMP-8 and MMP-13), gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3 and MMP-10). 20 Several nonsecreted MMPs are bound to membranes and designated MT-MMPs. 25 Tumor spread is a multistep process, which requires degradation or breakdown of the ECM and connective tissue and is caused by the concerted effects of these MMPs. 26 In the initial stage of tumor invasion, the gelatinases, particularly MMP-2, degrade components of the basement membrane, including type IV collagen. Although MMP-3, one of the stromelysins, also breaks down type IV collagen of the basement membrane, it degrades a variety of matrix components, including proteoglycans and noncollagenous glycoproteins such as laminin and fibronectin. Local tumor invasion is facilitated by collagenases, particularly MMP-1, which degrades the ECM. 20 MT1-MMP triggers tumor invasion by activating MMP-2. 25,27,28 Cutaneous MM is characterized by a high potential for invasion and metastasis. Previous studies reported the involvement of MMPs in migration, invasion, metastasis and progression of MM. Elevated expression of MMP-1, MMP-2 or MMP-9 was correlated with migration and invasion of cultured human melanoma cells. 21,22,29,30 In human melanoma lesions, positive correlations between tumor progressio...

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas

“…The result is increased production of factors that participate in tumor virulence by promoting, for example, angiogenesis and degradation of the extracellular matrix. 5,28 Our finding of increased matrix metalloproteinase-2 staining in tumor cells near the inflammatory infiltrate is consistent with the literature and suggests that matrix metalloproteinase-2 may interact with the inflammatory infiltrate to further cutaneous squamous cell carcinoma progression.…”

“…Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ lesions. 4,5 Matrix metalloproteinase-2 has affinity for gelatin; collagen I, IV, VII, X; tenascin; fibrillin; osteonectin; fibronectin; and monocyte chemoattractant protein 3. 1 Collagenase IV activity is particularly associated with basement membrane compromise.…”

High incidence of EMMPRIN expression in human tumors

“…However, conflicting results regarding the putative involvement of EMMPRIN in the progression of melanomas were reported, implying that a more detailed analysis of EMMPRIN expression in human melanomas need to be conducted. 36,37 Our findings showed that many malignant tumors with a high incidence of EMMPRIN expression, such as, for example, head and neck SCCs or glioblastomas, are known to frequently overexpress EGFR, 38,39 suggesting that there might be a functional link between these 2 cell surface receptors. Indeed, evidence was provided that in immortalized NS2T2A1 breast cells EMMPRIN expression is induced by activation of EGFR through its ligand amphiregulin.…”

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

“…CD147 expression is elevated on several human tumors and has been correlated with the malignancy in some cancers such as primary breast cancer and ovarian cancer, etc. (7)(8)(9)(10)(11)(12). Despite the close correlation between CD147 expression and malignancy of some tumors, it is not clear whether CD147 has a functional role in tumor genesis and hepatocellular carcinoma (HCC) progression.…”