Role Of CD147 Research Articles

The protein-interaction network with functional roles in tumorigenesis, neurodegeneration, and aging.

The present review summarizes the knowledge about a protein-interaction network, which includes proteins with significant functions in the mechanisms of aging and age-related diseases. All the detected interacting proteins TPPII, p53, MYBBP1A, CDK2 and SIRT7, SIRT6, and CD147 are suitable for the development of antitumor therapeutics and treatments for diseases of aging. TPPII and SIRT6 directly affect glucose metabolism which drive malignant growth. In addition, SIRT6 activators are attractive candidates for Alzheimer's disease (AD) due to the protection effect of SIRT6 overexpression from DNA damage. TPPII activity exhibits a decreasing effect on mTOR signaling, and its requirement for the degradation of Aβ peptides in the human fibroblasts suggests that it has dual functions in tumorigenesis and AD-related pathology. Likewise, the direct promotion of the invasiveness of breast epithelial cells and the contribution to the Aβ degradation by stimulating the matrix metalloproteinases production suggest a double functional role for CD147. An association of the partial portion of cellular CD147 to γ-secretase further supports the functional relation to AD pathology. The animal and cellular models with downregulated or knockout TPPII, p53, SIRT6, SIRT7, and MYBBP1A expression levels illustrate similar functions of the interacting proteins. They demonstrate similar effects on the length of life span, premature aging, and lipid metabolism. The presented protein-interaction network is relevant to the discoveries of the mechanisms of tumorigenesis, aging, and neurodegeneration.

Basic Science Liver.

Basic Science Liver.

The Multistep Functions of EMMPRIN/ CD147 in the Tumor Angiogenesis

CD147 is a member of the immunoglobulin family of receptors. Both clinical studies and basic research have indicated that elevated CD147 expression is correlated with tumor progression. It facilitates cancer invasion and angiogenesis. Targeting CD147 in cancer appears a promising future therapeutic strategy, but requires a better understanding of its mode of action and regulation. This review focuses on the most recent findings that addressing the role of CD147 in tumor angiogenesis and highlight the relational mechanisms. Supporting these findings are evidences that CD147 is an important modulator in tumor angiogenesis, thus, more attractive as a target for anti-tumor treatment.

CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells

The multifunctional glycoprotein cluster of differentiation (CD)147 is highly expressed on the cell surface of the majority of cancer cells, and promotes tumor invasion, metastasis and growth. However, the role of CD147 in autophagy has not yet been explored in prostrate cancer cells. In the present study, prostate cancer PC-3 cells were cultured under starvation conditions, and the expression level of CD147 gradually increased. Therefore, RNA interference was used to inhibit CD147 expression, in order to investigate the biological role of this glycoprotein in autophagy progression. Autophagic activity was monitored by the changes in green fluorescent protein-light chain 3 (GFP-LC3) location and the expression of the autophagy-associated protein LC3-II. It was found that downregulation of CD147 significantly promoted GFP-LC3 puncta formation and the expression of LC3-II. Furthermore, the levels of phosphorylated serine/threonine protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR) were significantly decreased, and the level of LC3-II was inversely associated with levels of p-Akt and p-mTOR in cells with downregulated expression of CD147. The results of a trypan blue exclusion assay revealed that starvation-induced cell death was increased in PC-3/shCD147 cells compared with control PC-3/Scramble cells (37.7±6.4 vs. 21.7±5.5%). Together, these results indicate that CD147 may be important in the inhibition of autophagy via the PI3K/Akt/mTOR pathway, which prevents cell death from unrestrained autophagy.

Abstract LB-25: CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway

Abstract Background & Aims: Cancer cells exhibit the reprogrammed metabolism characterized by high level of glycolysis even in the presence of oxygen. Aerobic glycolysis, known as the Warburg effect, supplys cancer cells with the substrates required for biomass generation. To date, several intracellular signaling mediators have been identified in metabolic regulation of cancer cells. However, it remains largely ambiguous how molecules on cell surface are involved in regulation of cancer metabolism. Methods: In the current study, we established several HCC cell lines differing in their CD147 (a typical transmembrane glycoprotein) expression status by zinc-finger nuclease and RNAi techniques. Then, we systematically investigated the role of CD147 in the regulation of Warburg effect in HCC cells and explored the underlying mechanism. Results: We found that CD147 significantly contributed to the reprogramming of glucose metabolism in HCC cells through a p53-dependent way. CD147 facilitated the cell surface expression of MCT1 and lactate export, which led to the activation of PI3K/Akt/MDM2 pathway and thus increased p53 degradation. The gain/loss-of-function studies demonstrated that while CD147 promoted glycolysis mediated by p53-dependent up-regulation of GLUT1 and activation of PFKL; it inhibited mitochondrial biogenesis and functions mediated by p53-dependent down-regulation of PGC1α, TFAM and P53R2. Additionally, proliferation of HCC cells was suppressed by blocking CD147 and/or MCT1 which resulted in down-regulation of glucose metabolism. Conclusions: we demonstrate that CD147 is a crucial regulator of glucose metabolism. Citation Format: Qichao Huang, Jibin Li, Jinliang Xing. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting p53-dependent signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-25. doi:10.1158/1538-7445.AM2014-LB-25

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4+ T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration.

Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis.

BackgroundThe classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC.MethodsNon-diseased, fibrotic and cirrhotic livers were examined for MMP activity and markers of fibrosis in humans and mice. CD147 expression and MMP activity were co-localised by in-situ zymography. The role of CD147 was studied in-vitro with siRNA to CD147 in hepatocytes and in-vivo in mice with CCl4 induced liver injury using ãCD147 antibody intervention.ResultsIn liver fibrosis in both human and mouse tissue MMP expression and activity (MMP-2, -9, -13 and -14) increased with progressive injury and localised to hepatocytes. Additionally, as expected, MMPs were abundantly expressed by activated HSC. Further, with progressive fibrosis there was expression of CD147, which localised to hepatocytes but not to HSC. Functionally significant in-vitro regulation of hepatocyte MMP production by CD147 was demonstrated using siRNA to CD147 that decreased hepatocyte MMP-2 and -9 expression/activity. Further, in-vivo α-CD147 antibody intervention decreased liver MMP-2, -9, -13, -14, TGF-β and α-SMA expression in CCl4 treated mice compared to controls.ConclusionWe have shown that hepatocytes produce active MMPs and that the glycoprotein CD147 regulates hepatocyte MMP expression. Targeting CD147 regulates hepatocyte MMP production both in-vitro and in-vivo, with the net result being reduced fibrotic matrix turnover in-vivo. Therefore, CD147 regulation of hepatocyte MMP is a novel pathway that could be targeted by future anti-fibrogenic agents.

Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis

Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis.

CD147 Promote Proliferation in Prostate Cancer Cell

CD147 is expressed on the cell surface of most tumor cells, which results in cancer cells proliferation, invasion, metastasis and angiogenes. Our previous study indicated that CD147 could promote invasion andmetastasis of prostate cancer. However the role of CD147 on cell proliferation has not to be explored inprostate cancer. In this study, the effects of CD147 on cell proliferation of hormone-independent prostatecancer (LNCaP-AI) was investigated. In the present study, cell cycle distribution was investigated by flowcytometry and cell cycle protein were analysis by wester blot. The results demonstrated that knock-donwn CD147 expression induced G0/G1 phase arrest, and expression of cyclin D1 has potential suppressed with western blot analysis. The results suggest that CD147 could inhibit cell prolifearion and as potential therapeutic application in treatment of proste cancer.

The roles of CD147 and/or cyclophilin A in kidney diseases.

CD147 is a widely expressed integral plasma membrane glycoprotein and has been involved in a variety of physiological and pathological activities in combination with different partners, including cyclophilins, caveolin-1, monocarboxylate transporters, and integrins. Recent data demonstrate that both CyPA and CD147 significantly contribute to renal inflammation, acute kidney injury, renal fibrosis, and renal cell carcinoma. Here we review the current understanding of cyclophilin A and CD147 expression and functions in kidney diseases and potential implications for treatment of kidney diseases.

Identification of CD147 (basigin) as a mediator of trophoblast functions

Does CD147 regulate trophoblast functions in vitro? CD147 exists as a receptor complex on human trophoblast and regulates the implantation, invasion and differentiation of trophoblast. CD147 is a membrane protein implicated in a variety of physiological and pathological conditions due to its regulation of cell-cell recognition, cell differentiation and tissue remodeling. Reduced placental CD147 expression is associated with pre-eclampsia, but the mechanism of actions remains unclear. A loss of function approach or functional blocking antibody was used to study the function of CD147 in primary human cytotrophoblasts isolated from first trimester termination of pregnancy and/or in the BeWo cell line, which possesses characteristics of human cytotrophoblasts. CD147 expression was analyzed by immunofluorescence staining and western blotting. CD147-associated protein complex on plasma membrane were separated by blue native gel electrophoresis and identified by reversed-phase liquid chromatography coupled with quadrupole time-of-flight hybrid mass spectrometer. Cell proliferation and invasion were determined by fluorometric cell proliferation assays and transwell invasion assays, respectively. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) activities were measured by gelatin gel zymography and uPA assay kits, respectively. Cell migration was determined by wound-healing assays. Cell fusion was analyzed by immunocytochemistry staining of E-cadherin and 4',6-diamidino-2-phenylindole. The transcripts of matrix proteinases and trophoblast lineage markers were measured by quantitative PCR. Extracellular signal-regulated kinase (ERK) activation was analyzed by western blot using antibodies against ERKs. CD147 exists as protein complexes on the plasma membrane of primary human cytotrophoblasts and BeWo cells. Several known CD147-interacting partners, including integrin β1 and monocarboxylate transporter-1, were identified. Suppression of CD147 by siRNA significantly (P < 0.05) reduced trophoblast-endometrial cell interaction, cell invasion, syncytialization, differentiation and ERK activation of BeWo cells. Consistently, anti-CD147 functional blocking antibody suppressed the invasiveness of primary human cytotrophoblasts. The reduced invasiveness was probably due to the restrained (P < 0.05) enzyme activities of MMP-2, MMP-9 and uPA. Most of the above findings are based on BeWo cell lines. These results need to be confirmed with human first trimester primary cytotrophoblast. This is the first study on the role of CD147 in trophoblast function. Further investigation on the function of CD147 and its associated protein complexes will enhance our understanding on human placentation. This work was supported in part by the University of Hong Kong Grant 201011159200. The authors have no competing interests to declare.

Abstract 887: Novel role of CD147 in chemoresistance in pancreatic cancer.

Abstract Pancreatic cancer is the fourth leading cause of cancer mortality in the U.S. with only a 25% one-year survival rate and 100% mortality rate. No favorable therapeutic strategy has been established in recurrent pancreatic cancer. The cell surface protein CD147 is a glycoprotein and plays a central role in chemoresistance of pancreatic cancer and its upregulation indicates poor prognosis. However, the mechanism by which this protein is involved in pancreatic cancer is still poorly understood. Here we show that knockdown of CD147 in pancreatic cancer cells decelerates tumor growth and sensitizes cells to chemotherapeutic drugs. To identify the mechanisms involved in the slow growth, we screened several genes using a luciferase method. We found that knockdown of CD147 leads to decreased transcription of several genes involved in cancer progression such as telomerase and VEGFC. Knockdown of CD147 leads to high sensitivity of pancreatic cancer cells to chemotherapeutics such as gemcitabine and doxorubicin. Interestingly, the metastatic cell line, L3.6pL, is more sensitive to both chemotherapeutic drugs than the non-metastatic cell line, Panc-1. CD147 knockdown also leads to less drug efflux than control as detected by rhodamine assay. Our hypothesis is that CD147 may interact and block some membrane transporters, which lead to an increase of intracellular drug and therefore to chemosensitivity. We analyzed the transcriptional activity of several membrane transporters including ABCC5, ABCC10 and ABCA2. We found that there is a decrease in their transcription levels of approximately 50% compared to the control. This may suggest that CD147 is involved in drug transport through the cytoplasmic membrane. We have also determined that depleting CD147 leads to an increase of sensitivity in pancreatic cancer cells to chemotherapeutic drugs such as doxorubicin and gemcitabine. Gemcitabine can create DNA damage such as double stand breaks in cells, followed rapidly by histone H2AX phosphorylation (𝛄H2AX), with foci observed within the first minute. Using CD147 knockdown cells, we showed that knockdown of CD147 leads to the depletion of H2AX phosphorylation and to an increase of apoptosis, in agreement with high drug accumulation. We found high ROS levels in these cells as measured by the DCF using flow cytometry. This can explain an increase of apoptosis in cells with CD147 knockdown. Our results indicate that CD147 acts to enhance tumor growth in several ways and contributes to chemoresistance in pancreatic cancer. We explored the mechanism of action of CD147, which can be a potential novel therapeutic target in pancreatic cancer. Citation Format: Karim Bahmed, Michael Holliday, Agnieszka Kendrick, Elan Eisenmesser. Novel role of CD147 in chemoresistance in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 887. doi:10.1158/1538-7445.AM2013-887

EMMPRIN/CD147 expression is associated with disease-free survival of patients with colorectal cancer

EMMPRIN/CD147 has been proved to be associated with tumor invasion and metastasis in various human malignancies. In the present study, we investigated the expression of CD147 and its association with disease-free survival of colorectal cancer patients. CD147 expression was investigated in 328 cases of colorectal cancer by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of CD147 expression with disease-free survival of colorectal cancer patients. CD147 expression was proved to be increased in colorectal cancer (P < 0.001) and related to tumor invasion (P < 0.001), metastasis (P < 0.001), and TNM stage (P < 0.001). Kaplan-Meier showed CD147 was associated with disease-free survival of patients with colorectal cancer for patients with higher CD147 expression tend to have shorter disease-free survival (P < 0.001). Multivariate analysis also proved CD147 to be an independent prognostic factor for disease-free survival of colorectal cancer patients (P < 0.05). These results suggested the potential role of CD147 in relapse of human colorectal cancer. It might be a novel molecular marker to predict relapse of patients with colorectal cancer.

The Role of CD147 in the Invasiveness of Follicular Thyroid Carcinoma Cells

In patients without metastases, capsular and vascular invasion must be noted to make the diagnosis of follicular thyroid carcinoma (FTC). Some patients are initially diagnosed as follicular adenoma (FA) but develop metastases, indicating the original lesion was FTC. A diagnostic marker for FTCs that appear to be FAs by conventional histopathology is urgently needed. CD147 is a transmembrane glycoprotein that induces matrix metalloproteinases (MMPs) and participates in carcinoma invasion. The objective of this study was to determine whether CD147 is upregulated in FTC and if measures directed against it could reduce the invasive activity of FTC cells. The expression levels of CD147, MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9 in surgical specimens of normal thyroid (n=8), FA (n=20), and FTC (n=9) was determined using immunoblot and immunohistochemical techniques. CD147 protein expression levels of epithelial growth factor stimulated FTC-133 cell lines was measured by immunoblotting with and without cell signaling inhibitors such as wortmannin, PD98059, SP600125, and SB203580. This was also done after exposure to short-hairpin interference RNA directed against CD147. Immunoblot analysis of thyroid tissues revealed significant increases in signals for CD147, MMP-3, MMP-7, and MMP-9 in FTC compared with FA or normal tissue, or both. Immunohistochemical analysis revealed colocalization of determinants of CD147 with those of all of MMPs studied, mainly in follicular cells in normal and neoplastic cells in FA and FTC; their immunoreactivities were to some extent more intense in the FTC than FA or normals. In FTC-133 cells, immunoreactive signals for CD147 were upregulated by epidermal growth factor (EGF), and the EGF-driven increases in CD147 were prevented by inhibitors against phosphoinositol-3 kinase (PI3K), extracellular signal-regulated protein kinase (ERK), or c-Jun N-terminal kinase (JNK) but not p38. RNA interference targeted against CD147 reduced the invasive activity of FTC-133 cells and was associated with downregulation of MMP-2, MMP-3, MMP-7, and MMP-9. These results provide in vivo evidence for CD147 upregulation in FTC and in vitro evidence for EGF-stimulated CD147 induction via the PI3K, ERK, and JNK pathways. They suggest the involvement of CD147 in the invasiveness of FTC cells via regulation of MMPs.

Involvement of CD147 isoform‑4 in the proliferation of SiHa cells: A possible molecular mechanism of cervical cancer

CD147, a multifunction glycoprotein of the immuno-globulin family, is associated with many types of tumors, and the overexpression of CD147 can enhance malignancy. However, the role of CD147 in cervical cancer remains unclear. In the present study, cervical cancer cells were found to express much more CD147 protein and isoform‑4 than normal cervical cells (P<0.05), suggesting that CD147 and isoform‑4 are involved in cervical cancers. Furthermore, we overexpressed the CD147 isoform‑4 (CD147‑4) in the cervical cancer cell line SiHa by transfection and found that CD147-4 promoted the proliferation of SiHa cells with a considerable proportion of cells in the Sphase in which the expression of CIP2A, Plk and cyclinD1 was up-regulated while the expression of P27 was down-regulated. This may be one of the molecular mechanisms involved in cervical cancer progression by CD147.

Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to cisplatin in laryngeal carcinoma Hep2 cells

CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), is a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, which promotes invasion, metastasis, growth and survival of malignant cells, and is known to confer resistance to some chemotherapeutic drugs. To determine the possible role of CD147 in the invasive properties of laryngeal carcinoma, we used an RNA interference approach to silence CD147 expression in the Hep2 cell line at high levels of CD147 expression. Our results showed that CD147 expression was significantly impeded at both mRNA and protein levels, which resulted in a decrease of the Hep2 invasion activity in vitro and tumorigenicity in nude mice. The suppression of CD147 expression also sensitized cells to cisplatin. Our current results indicated that CD147 was a laryngeal carcinoma-related gene and CD147 might be a potential target for therapeutic anti-cancer drugs.

CD147 and VEGF Co-expression Predicts Prognosis in Patients with Acute Myeloid Leukemia

To investigate the possible role of CD147 and vascular endothelial growth factor in progression and prognosis of acute myeloid leukemia. Immunohistochemical staining was performed to detect the expression of CD147 and vascular endothelial growth factor in paraffin-embedded sections from 62 bone marrow biopsies obtained from an equal number of patients with newly diagnosed acute myeloid leukemia. CD147 and vascular endothelial growth factor expression in the bone marrow of acute myeloid leukemia patients were significantly higher than those in normal controls (both P < 0.001). Expression of them was significantly increased in patients with a high degree of microvessel density compared with those with a low degree (CD147: P = 0.009; vascular endothelial growth factor: P = 0.01) and correlated well with bone marrow microvessel density (CD147: P = 0.01; vascular endothelial growth factor: P = 0.02). In addition, higher levels of CD147 and vascular endothelial growth factor were also found in acute myeloid leukemia patients with an unfavorable karyotype compared with those with intermediate and favorable karyotypes (both P = 0.01). Moreover, the expression of CD147 was significantly correlated with that of vascular endothelial growth factor (P < 0.001). Furthermore, the co-expression of CD147 and vascular endothelial growth factor in the bone marrow indicated a poor prognosis in acute myeloid leukemia and was an independent prognostic factor for overall survival by multivariate analysis. Our data show for the first time that the co-expression of CD147 and vascular endothelial growth factor may indicate a poor prognosis in acute myeloid leukemia and may be a highly sensitive marker for predicting the clinical outcome of patients.

RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro

BackgroundCD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer.MethodsShort hairpin RNA (shRNA) expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively.ResultsDown-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin.ConclusionCD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.

Vasculogenic mimicry of human ovarian cancer cells: Role of CD147

The term vasculogenic mimicry (VM) indicates the process by which aggressive tumor cells are able to generate in vitro non-endothelial cell-lined channels delimited by extracellular matrix. Although VM has been described in several human malignancies, the molecular basis of this phenomenon is not entirely understood. In the present study, we examined VM in two ovarian cancer cell lines with different invasion capability (CABA I, low invasion activity; SKOV3, high invasion activity). Specifically, we focused on the potential role played by CD147/extracellular MMP inducer, a membrane spanning molecule highly expressed in tumor cells, in VM. Previous studies have shown that CD147 may be involved in the progression of malignancies by regulating the expression of metalloproteinases in peritumoral stromal cells. In this study, we found significant correlations between expression of CD147 in ovarian cancer cell lines and tumor invasiveness, the activity of the proteases and the ability to form vascular channels. The treatment of SKOV3 cells with small interfering RNA against CD147 suppressed the ability of these cells to generate non-endothelial cell-lined channels. In contrast, transfection of CD147 cDNA into the CABA I cell line resulted in an increased tumor invasiveness and enabled the formation of vascular channels. Altogether, our data suggest that CD147 may play a critical role in VM of CABA I and SKOV3, human ovarian cancer cell lines.

CD147 silencing inhibits lactate transport and reduces malignant potential of pancreatic cancer cells in in-vivo and in-vitro models

Background: CD147 (basigin, EMMPRIN) is a multifunctional, highly conserved glycoprotein enriched in pancreatic ductal adenocarcinomas (PDACs) which is associated with poor prognosis in many malignancies. The role of CD147 in pancreatic cancer, however, remains elusive. Methods and Results: Silencing of CD147 by RNA interference (RNAi) reduced the proliferation rate of MiaPaCa2 and Panc1 cells. CD147 is required for the function and expression of the monocarboxylate transporters MCT1 and MCT4 that are expressed in human PDAC cells as demonstrated by real-time reverse transcription-PCR (RT-PCR) as well as immunohistology. MCT1 and MCT4 are the natural transporters of lactate, and MiaPaCa2 cells exhibited a high rate of lactate production, which is characteristic for the Warburg effect, an early hallmark of cancer that confers a significant growth advantage. Further induction of lactate production by sodium azide in MiaPaCa2 cells increased MCT1 as well as MCT4 expression. CD147 silencing inhibited the expression and function of MCT1 and MCT4 and resulted in an increased intracellular lactate concentration. Addition of exogenous lactate inhibited cancer cell growth in a dose-dependent fashion. In vivo, knock-down of CD147 in MiaPaCa2 cells by inducible short hairpin RNA (shRNA)-mediated CD147 silencing reduced invasiveness through the chorioallantoic membrane of chick embryos (CAM assay) and inhibited tumourigenicity in a xenograft model in nude mice. Conclusion : The function of CD147 as an ancillary protein that is required to sustain the expression and function of MCT1 and MCT4 is involved in the association of CD147 expression with the malignant potential of pancreatic cancer cells exhibiting the Warburg effect.