Overexpression of CD147 contributes to the chemoresistance of head and neck squamous cell carcinoma cells

Abstract

Head and neck cancer is the sixth most common cancer in the world and most of them are squamous cell carcinomas. High frequency of cisplatin resistance in head and neck squamous cell carcinoma (HNSCC) leads to tumor relapse and irresponsiveness to cisplatin-based chemotherapy. However, the mechanisms underlying cisplatin resistance is still largely unrevealed. In this study, we found that CD147 was overexpressed in cisplatin-resistant HNSCC cell lines. Based on the result, CD147 expression was down-regulated in the cisplatin-resistant cell line and we observed that the sensitivity to cisplatin increased, as showed in the results of MTT assay and PI-staining apoptotic detection. Meanwhile, transfection of CD147 expression vector promoted the occurrence of cisplatin resistance in the cisplatin-sensitive cell line. Simultaneously blocking of uPAR with neutralizing antibody would significantly prevent the occurrence of cisplatin resistance induced by CD147 overexpression. In conclusion, our study finds that CD147 is also involved in mediating cisplatin resistance in HNSCC and uPAR serves as a possible candidate that collaborates with CD147 in this process.

EMMPRIN Expression in Oral Squamous Cell Carcinomas: Correlation with Tumor Proliferation and Patient Survival

“…This could be an important result suggesting the use of this receptor as a prognostic biomarker in OSCC. Interestingly, some studies report that EMMPRIN might be even a predictive marker of chemoresistance in head and neck carcinomas [8]. The influence of this receptor on patient's prognostic could be related to the multiple biological functions of this protein on tumor cells such as proliferation, migration, invasion, angiogenesis, and dissemination on OSCC [4].…”

“…EMMPRIN is expressed in several cancers including head and neck squamous-cell carcinomas, pancreatic adenocarcinomas, kidney chromophobic carcinomas, hepatocellular carcinomas, medullary breast adenocarcinomas, cervix carcinomas, and glioblastomas [5]. EMMPRIN contributes to cell adhesion modulation, tumor growth, invasion, and angiogenesis [4–7] probably due to its association with several proteins implicated in different signaling pathways such as matrix metalloproteinases, ErbB, MAPK cascade proteins, monocarboxylate transporters (MCT), integrins, caveolin-1 (Cav-1), Tenascin (TN)-C, vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), and cyclophilins (Cyp) [4, 6, 8, 9]. …”

The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature

“…Furthermore, CD147 and LYVE-1 coregulate the chemoresistance of KSHV-infected lymphoma cells [71]. Using a neutralizing antibody to uPAR could down-regulate the HNSCC resistance to cisplatin induced by CD147 over-expression, resulting in increased HNSCC sensitivity to cisplatin, which may indicate that CD147 and uPAR collaborate in the chemoresistance process [148]. The inhibition of CD147, P-gp, and p-Akt by STAT3 decoy oligodeoxynucleotide (ODN) technology inhibits ovarian cancer cell invasiveness and enhances the paclitaxel sensitivity of SKOV3 and OVCAR3 ovarian cancer cells [149].…”

Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status

“…It is a widely distributed heavily glycosylated type I transmembrane glycoprotein [14, 15] and is expressed at high levels mainly in metabolically active cells such as lymphoblasts and malignant tumour cells [9, 37, 40]. BSG has been proposed to effect metalloproteinases (MMP) that degrade the extracellular matrix [37], tumour growth, chemoresistance [12, 13, 41, 42] and metastasis [22, 37]. However, the role of MCTs/BSG in lung cancer is controversial and poorly elucidated [16, 20, 27].…”