VCAM-1 (CD106) is a transmembrane glycoprotein and involved in many pathological inflammatory processes. VCAM-1 plays an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (£\4£]1). In our preliminary data, we observed 2-3 fold increase in the expression of VCAM-1 in the side population of ovarian cancer, which exhibits stem cell-like properties in ovarian cancer. In addition, we have also found VCAM-1 is upregulated in many breast cancer epithelial cells and directly correlated with breast tumor progression; however, its mechanism of action in tumor biology remains unknown. Here, we describe the establishment and use of breast cancer cell line model systems to dissect the functional roles of VCAM-1 activation in the manifestation of malignant phenotype of human breast cancer. We show that VCAM-1 overexpression in the NMuMG breast epithelial cells increase cell motility rates and chemoresistance to doxorubicin and cisplatin in vitro, conversely, in an established metastatic breast cancer cell line, MDAMB231, we find that knockdown endogenous VCAM-1 expression by small interfering RNA reduced the migration rate . Furthermore, we also demonstrated that knockdown endogenous VCAM-1 expression in MDAMB231 cells reduced the tumor formation in SCID xenograft mouse model. In conclusion, our findings are consistent with the hypothesis that overexpression of VCAM-1 facilitates breast cancer progression by enhancing the malignant properties of breast cancer cells and suggests that targeting of VCAM-1 induced pathways are attractive strategies for therapeutic intervention.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0803110-111643 |
| Date | 03 August 2010 |
| Creators | Wang, Pei-chen |
| Contributors | Hurng-wern Hunang, Kuang-hung Cheng, Long-sen Chang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0803110-111643 |
| Rights | not_available, Copyright information available at source archive |
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