Cluster of differentiation 147(CD147)/extracellular matrix metalloproteinase inducer (EMMPRIN) is a widely distributed transmembrane glycoprotein that belongs to the immunoglobulin superfamily and is highly enriched on the surface of malignant tumour cells. A major function of CD147 is to stimulate matrix metalloproteinase production in stromal fibroblasts and endothelial cells. CD147 promotes growth,invasion,metastasis,and glycolysis of malignant cells,induces angiogenesis,multidrug resistance,and anoikis resistance,and inhibits starvation-induced autophagy et al. This review focuses on the structural and biological characteristics of CD147 as well as recent advances in its multiple functions in malignant tumours and underlining mechanisms.
Basigin ; metabolism ; Fibroblasts ; Humans ; Neoplasms ; metabolism ; Neovascularization, Pathologic

CD147 (basigin, EMMPRIN, neurothelin, M6, HAb18G, etc.), a transmembrane glycoprotein, has a broad expression pattern on various epithelial cells with some differences between species, e.g. rat, mouse, chicken and human, but is highly enriched on the surface of cancer cells of epithelial origin such as lung cancer, breast cancer and hepatoma cells. The CD147 antigen consists of two IgSF domains, a transmembrane sequence containing a charged residue (Glu) and a cytoplasmic domain of 40 residues. The particular structural features suggest that it is involved in protein-protein interactions. Although the interacting molecules are still not well known due to unavailability of the 3D structure of CD147, adhesion, coimmunoprecipitation and other studies recently suggest that several proteins, including integrins, cyclophilins, MCT, etc., interact with CD147 as its ligand or receptor candidates to mediate a wide range of cellular functions.
Animals ; Basigin ; physiology ; Chickens ; Humans ; Mice ; Protein Conformation ; Rats

OBJECTIVETo investigate whether miR-492 is involved in the post-transcriptional regulation of OK blood group antigen expression on red blood cells.

METHODSTwo 3'-UTR fragments of the BSG gene were synthesized with a chemical method, which respectively encompassed the BSG rs8259 TT or BSG rs8259 AA sites. The fragments were added with Xho I and Not I restriction enzyme cutting sites at both ends and cloned into a pUC57 vector, which in turn was constructed into a psiCHECK-2 vector and verified by sequencing. K562 cells were transfected with various combinations of miR-492 mimic and constructed psiCHECK2-BSG-T or psiCHECK2-BSG-A recombinant plasmid. A blank control group was set up. Each transfection experiment was repeated three times. The activity of Renilla reniformis luciferase was determined and normalized with that of firefly luciferase, and detected with a dual-luciferase reporter assay system. The data were subjected to statistical analysis.

RESULTSThe sequencing results confirmed that the recombinant psiCHECK2 plasmids containing the BSG rs8259 TT or rs8259 AA sites were constructed successfully. The results of dual-luciferase report gene detection showed that the miR-492 mimic could significantly inhibit psiCHECK2-BSG-T at a concentration over 100 nmol/L. However, it could not inhibit psiCHECK-BSG-A.

CONCLUSIONmiR-492 may be involved in the regulation of OK antigen expression on red blood cells with the BSG rs8259 TT genotype.

Basigin ; genetics ; Blood Group Antigens ; genetics ; Erythrocytes ; immunology ; Gene Expression Regulation ; Genotype ; Humans ; MicroRNAs ; physiology

OBJECTIVES: To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line. METHODS: The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl RESULTS: HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl CONCLUSIONS Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.
Basigin ; Glucose Transporter Type 1 ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Psoriasis/genetics* ; Transcriptional Activation ; Up-Regulation

OBJECTIVETo investigate the expression of extracellular matrix metalloproteinase inducer gene (EMMPRIN) regulated by the interactions between fibroblasts and colon cancer cells, and to study its role in the invasion and metastasis of colon cancer.

METHODSColon cancer cells (SW480) were co-cultured with fibroblasts (HELF) in RPMI 1640 media for 0, 12, 24 and 48 hours. The expression of EMMPRIN in SW480 cells and HELF cells was documented by RT-PCR and immunocytochemistry.

RESULTSThe mRNA and protein expressions of EMMPRIN in SW480 cells were remarkably increased by the co-culturing with HELF cells. Although without the endogenous expression, HELF cells began to express EMMPRIN in a time-dependent manner after being co-cultured with SW480 cells.

CONCLUSIONSIntercellular interactions between colon cancer cells and fibroblasts not only up-regulate the EMMPRIN expression in SW480 cells, but also induce its expression in HELF cells. Such interactions may play a crucial role in the invasion and metastasis of colon cancer.

Basigin ; biosynthesis ; genetics ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Colonic Neoplasms ; metabolism ; pathology ; Fibroblasts ; cytology ; metabolism ; Humans ; Lung ; cytology ; RNA, Messenger ; metabolism

OBJECTIVETo screen out the HAb18G/CD147 binding peptides and find out an antagonist against hepatoma invasion.

METHODSHAb18G/CD147 was purified by affinity chromatographic method and the antigen binding peptides acquired by bio-panning a phage-displayed 12-peptide library. After obtaining the sequence of the selected phage-displayed peptides, all the 9 peptides were synthesized by solid-phase method and identified by mass spectrograph. The peptides' anti-metastatic function was tested by Boyden Chamber assay.

RESULTSThe purified HAb18G/CD147, identified by Western blot (molecular weight about 65 kd) could be used to bio-pan the phage-displayed peptide library. After 3 rounds of bio-panning, 9 positive phage clones were selected and sequenced. The synthesized peptides had uneven inhibitory activities and three of them were able to markedly inhibit the hepatoma cell invasion (P < 0.01). The most effective peptide decreased by 90.1% of hepatoma cells migrating through the Boyden Chamber membrane as compared with the control.

CONCLUSIONBio-panning the phage-displayed peptide library can be used successfully to screen out the antigen binding peptides. Hepatoma metastatic potential can be inhibited by peptide antagonist which could be a good foundation of developing peptide therapeutic agent against hepatoma metastasis.

Animals ; Antibodies, Monoclonal ; therapeutic use ; Basigin ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Mice ; Neoplasm Invasiveness ; Peptide Library ; Peptides ; therapeutic use

BACKGROUNDInteractions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 (CXCR4) and extracellular matrix metalloproteinase inducer (EMMPRIN) had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated.

METHODSA co-culture system between SHI-1 cells and bone marrow stromal cells (BMSCs) is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1:10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP-2), and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 (SDF-1) in serum free supernatant was measured by ELISA.

RESULTSBoth SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the coculture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant.

CONCLUSIONThe interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.

Basigin ; physiology ; Cell Communication ; Cell Line, Tumor ; Coculture Techniques ; Humans ; Leukemia, Monocytic, Acute ; pathology ; Mesenchymal Stromal Cells ; physiology ; Neoplasm Invasiveness ; Receptors, CXCR4 ; physiology

The aim of this study was to explore the molecular mechanisms of the effect of low intensity pulsed ultrasound (LIPUS) on human primary macrophage functions. Macrophage phagocytosis was analyzed using fluorescein isothiocyanate (FITC)-labelled Escherichia coli (E.Coli); focal complex and extracellular matrix metalloproteinase inducer (EMMPRIN) were observed by fluorescence microscopy; the secretion of metalloproteinases (MMPs) was examined by gelatin zymography, and the expressions of EMMPRIN and extracellular signal-regulated kinases (ERKs) were detected by Western blot. The results indicated that LIPUS accelerated macrophages to phagocytose E.Coli (29.81+/-0.36 vs 18.00+/-0.78), promoted the protein expressions of EMMPRIN and MMPs, increased the level of protein tyrosine phosphorylation, and induced the phosphorylation of ERKs. Furthermore, the above functions were only found in adherent macrophages, and were inhibited or decreased by mitogen activated protein kinase kinase (MAPK kinase, MEK) inhibitor PD98059 and RGD (Arg-Gly-Asp peptide), one of main integrin recognition sequences. It is concluded that the effect of LIPUS on macrophages depends on cell adhesion, and relates to integrin-MEK-ERK pathway.
Basigin ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; metabolism ; Humans ; Macrophages ; cytology ; immunology ; radiation effects ; Matrix Metalloproteinases ; metabolism ; Phagocytosis ; radiation effects ; Phosphorylation ; Ultrasonics

OBJECTIVETo investigate the association between CD147 expression and its untranslated regions 3'UTR rs8259 T/A polymorphism and acute coronary syndrome (ACS).

METHODSThe genotypes of CD147 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 182 ACS patients and 328 healthy controls. The plasma level of CD147 was determined by enzyme-linked immunosorbent assay (ELISA). CD147 mRNA and protein expression was detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot.

RESULTSThe plasma CD147 level obtained from radial artery in ACS patients ((3.63 ± 0.70) pg/L) was significantly higher than in control ((2.45 ± 0.27) pg/L, P < 0.05), and highest in plasma obtained from the coronary artery ((4.28 ± 1.03) pg/L, P < 0.05) in ACS patients. Furthermore, the plasma CD147 level was higher in the ACS patients with rs8259 AA genotype than in the ACS patients with rs8259 TT genotype ((4.08 ± 0.41) pg/L vs. (3.05 ± 0.79) pg/L in radial artery and (5.29 ± 0.62) pg/L vs. (3.13 ± 0.52) pg/L in coronary artery, both P < 0.05). There are an enhanced expression of CD147 mRNA (2.45 times higher than control) and protein (3.66 ± 1.56 vs. 1.81 ± 1.29) in PBMCs from ACS patients than that from controls (both P < 0.05). The PBMCs CD147 mRNA and protein expression level were significantly higher in ACS patients with rs8259 AA genotype (mRNA:2.45 ± 0.35, protein:1.63 ± 0.16) compared to ACS patients with rs8259 TT genotype (mRNA:1.69 ± 0.15, protein: 0.88 ± 0.16, both P < 0.05). Multiple logistic analysis showed that CD147 T allele (AT+TT) was a protective factor to ACS (OR = 0.667, 95% CI 0.507-0.879, P < 0.05).

CONCLUSIONSThe over-expression of CD147 is involved in the pathogenesis of ACS. The CD147 3'UTR rs8259 T allele may be a protective factor for ACS, its polymorphism can affect the CD147 protein expression in ACS patients.

Acute Coronary Syndrome ; genetics ; Alleles ; Basigin ; biosynthesis ; genetics ; Case-Control Studies ; Genotype ; Humans ; Leukocytes, Mononuclear ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the expression of CD147 and matrix metalloproteinase-9 (MMP-9) in children with non-Hodgkin's lymphoma (NHL) and its correlation with clinical stage, tumor size, bone marrow invasion, immunological typing, serum lactate dehydrogenase (LDH) concentration, and prognosis.

METHODSSpecimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by streptavidin-biotin complex (SABC) immunohistochemistry and its correlation with clinical results were analyzed.

RESULTSThe positive rate of CD147 expression was 73% (45/62), 17 cases were (-), 11 cases (+), 34 cases (++) and 21 cases (+++). The positive rate of MMP-9 expression was 81% (50/62), 12 cases were (-), 13 cases (+), 18 cases (++) and 19 cases (+++). The Spearman rank correlation analysis indicated that there was a positive correlation between CD147 and MMP-9 expressions in NHL (r(S) = 0.763, P = 0.034). Expression of CD147 was determined in relation to factors that included clinical bone marrow invasion, tumor size, LDH level as well as the clinical stage; expression of MMP-9 had a positive correlation with bone marrow invasion, tumor size and clinical phases. The 5-year survival rates (5YSR) were 78% (22/28) and 45% (15/34) in the cases whose CD147 expression was (-)-(+) and (++)-(+++), respectively, and 5YSR were 84% (21/25) and 43% (16/37) in the cases whose MMP-9 expression was (-)-(+) and (++)-(+++) respectively, the difference was significant. Cox multivariate analysis showed that both CD147 and MMP-9 were important prognostic factors.

CONCLUSIONThe increased expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.

Adolescent ; Basigin ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphoma, Non-Hodgkin ; diagnosis ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Prognosis ; Survival Rate