Caveolin-1 up-regulates CD147 glycosylation and the invasive capability of murine hepatocarcinoma cell lines.
CD147 which is a regulator of matrix metalloproteinase (MMP) production on the surface of many malignant tumor cells, shows a highly specific association with caveolin-1 (Cav-1). As a result of heterogeneous N-glycosylation, CD147 exists in both highly glycosylated form, HG-CD147 ( approximately 40-60kDa) and lowly glycosylated form, LG-CD147 ( approximately 32kDa). This study investigated the possible role of Cav-1 in CD147 glycosylation in the HcaF, HcaP and Hepa1-6 mouse hepatocarcinoma cell lines, which have high, low and no metastatic potential in the lymph nodes, respectively, and in the normal mouse liver cell line IAR-20. Using an RNA interference (RNAi) strategy, we showed that the down-regulation of Cav-1 in Hca-F/RNAi cells could suppress the conversion of LG-CD147 to HG-CD147, down-regulate MMP-11 expression and decrease Hca-F/RNAi cell invasion. Conversely, a stable high expression of Cav-1 in Hepa1-6/Cav-1 cell could cause a specific increase of HG-CD147, up-regulate MMP-11 protein expression and enhance Hepa1-6/Cav-1 cell invasion. In conclusion, Cav-1 expression leads to an increased proportion of HG-CD147 relative to LG-CD147, increased production of MMP-11 and a higher invasive capability. Cav-1 is therefore proposed to act as both an oncogene and a tumor suppressor gene, and could represent a new potential target for gene therapy.
Jia
Li
L
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 465 Zhongshan Road, Dalian 116027, Liaoning Province, China.
Wang
Shujing
S
Zhou
Huimin
H
Cao
Jun
J
Hu
Yichuan
Y
Zhang
Jianing
J
D000818:Animals; D051926:Basigin / Q000378:metabolism*; D051242:Caveolin 1 / Q000096:biosynthesis / Q000502:physiology*; D045744:Cell Line, Tumor; D006031:Glycosylation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D009361:Neoplasm Invasiveness; D015854:Up-Regulation
D051242:Caveolin 1; D051926:Basigin; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases