Matrix metalloproteinase-1 promotes prostate tumor growth and metastasis.
Cell migration and invasion are critical events during the progression to metastasis. Matrix metalloproteinase-1 (MMP-1) is involved in the progression of human malignancies, but the precise role of MMP-1 in tumor invasion and metastasis remains unclear. In the present study, we investigated the role of MMP-1 in tumor cell invasion and metastasis by overexpressing MMP-1 in prostate cancer cells. Overexpression of MMP-1 in prostate cancer cells increases cell invasion and migration as measured by modified transwell assays. Furthermore, the results from a bioluminescence tumor/metastasis model showed that the overexpression of MMP-1 significantly induces prostate tumor growth and the incidence of lung metastasis. We observed that this increase in tumor growth correlates with an increase in tumor angiogenesis. In addition, we assessed the importance of MMP-1 expression in cell invasion and migration by inhibiting MMP-1 activity with specific inhibitor and antibodies. Blockade of MMP-1 activity inhibited prostate cancer cell migration and invasion in vitro. Treatment of mice with an MMP-1 specific inhibitor significantly decreased prostate tumor growth and incidence of lung metastasis in vivo. Collectively, our findings suggest that MMP-1 plays an important role in prostate cancer progression during the invasive and metastatic stages of the disease.
Pulukuri
Sai Murali Krishna
SM
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, USA.
Rao
Jasti S
JS
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000209:etiology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000473:pathology*
D061965:Matrix Metalloproteinase Inhibitors; D020781:Matrix Metalloproteinase 1