Publicado 4 números por año
ISSN Imprimir: 0731-8898
ISSN En Línea: 2162-6537
Indexed in
Cell Membrane-Associated MT1-MMP Dependent Activation of MMP-2 in SiHa (Human Cervical Cancer) Cells
SINOPSIS
Among the soluble MMPs, MMP-2 (gelatinase A) is particularly important in the invasive property of tumor cells. Cell membrane-associated MMP-2 activation is one of the challenging areas in tumor biology. In the present communication, we studied the membrane dependent activation of MMP-2 in SiHa cells. Methods: Activation of pro-MMP-2 by membrane fraction, membrane extract, and live SiHa cells was studied by gelatin zymography. The role of MT1-MMP in MMP-2 activation was studied by incubating SiHa cells and cell membrane fractions with anti-MT1-MMP antibody. Results: Activation of purified pro-MMP-2 by membrane fraction isolated from SiHa cells, by SiHa cell membrane extract and by SiHa cells, pro-MMP-2 from Con A treated HT-1080 conditioned medium by SiHa cells, and pro-MMP-2 from serum free culture medium of SiHa cells and cervical tissue homogenate by SiHa cell membrane fraction was shown by gelatin zymography. SiHa membrane fraction activated only pro-MMP-2 from purified MMP-9/MMP-2 mixture, indicating that the activation is specific for MMP-2. Inhibition of MMP-2 activation in the presence of anti-MT1-MMP antibody strongly indicated that the cell membrane mediated MMP-2 activation is MT1-MMP dependent. Immunocytochemistry of SiHa cells demonstrated expression of MT1-MMP at focal points. Invasion assay showed that invasiveness of anti-MT1-MMP antibody treated SiHa cells through Matrigel was drastically reduced compared to control SiHa cells. Conclusions: Our findings furnish an example of the cell membrane-associated MT1-MMP mediated MMP-2 activation in SiHa cells and suggest that this MT1-MMP mediated MMP-2 activation is of importance in tumor invasion and metastasis. This MT1-MMP mediated MMP-2 activation on tumor cell surface could be a realistic target for managing metastatic diseases.
-
Lee Minnkyoung, Shimizu Emi, Krane Stephen M., Partridge Nicola C., Bone Proteinases, in Principles of Bone Biology, 2008. Crossref
-
Jorng-Tzong Horng , Kai-Chih Hu , Li-Cheng Wu , Hsien-Da Huang , Horn-Cheng Lai , Ton-Yuen Chu , Identifying the combination of genetic factors that determine susceptibility to cervical cancer, Proceedings. Fourth IEEE Symposium on Bioinformatics and Bioengineering, 2004. Crossref
-
Horng J.-T., Hu K.C., Wu L.-C., Huang H.-D., Lin F.-M., Huang S.L., Lai H.C., Chu T.Y., Identifying the Combination of Genetic Factors That Determine Susceptibility to Cervical Cancer, IEEE Transactions on Information Technology in Biomedicine, 8, 1, 2004. Crossref
-
Devy Laetitia, Dransfield Daniel T., New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies, Biochemistry Research International, 2011, 2011. Crossref
-
QI XIAORONG, DU LICHENG, CHEN XIANCHENG, CHEN LIJUAN, YI TAO, CHEN XIANG, WEN YANJUN, WEI YUQUAN, ZHAO XIA, VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein, International Journal of Oncology, 49, 1, 2016. Crossref
-
Nakatani Teruyo, Partridge Nicola C., Bone proteinases, in Principles of Bone Biology, 2020. Crossref
-
Chen Weiwei, Huang Shenjiao, Shi Kun, Yi Lisha, Liu Yaqiong, Liu Wenjie, Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis, Cancer Control, 28, 2021. Crossref
-
Azevedo Martins Jordana Maria, Rabelo-Santos Silvia Helena, do Amaral Westin Maria Cristina, Zeferino Luiz Carlos, Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis, BMC Cancer, 20, 1, 2020. Crossref