Assignment1: Citation

Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors

Abstract

Background: Cancer invasion and metastasis develops through a series of steps that involve the loss of cell to cell and cell to matrix adhesion, degradation of extracellular matrix and induction of angiogenesis. Different protease systems (e.g., matrix metalloproteinases, MMPs) are involved in these steps. MMP-10, one of the lesser studied MMPs, is limited to epithelial cells and can facilitate tumor cell invasion by targeting collagen, elastin and laminin. Enhanced MMP-10 expression has been linked to poor clinical prognosis in some cancers, however, mechanisms underlying a role for MMP-10 in tumorigenesis and progression remain largely unknown. Here, we report that MMP-10 expression is positively correlated with the invasiveness of human cervical and bladder cancers.

Methods: Using commercial tissue microarray (TMA) of cervical and bladder tissues, MMP-10 immunohistochemical staining was performed. Furthermore using a panel of human cells (HeLa and UROtsa), in vitro and in vivo experiments were performed in which MMP-10 was overexpressed or silenced and we noted phenotypic and genotypic changes.

Results: Experimentally, we showed that MMP-10 can regulate tumor cell migration and invasion, and endothelial cell tube formation, and that MMP-10 effects are associated with a resistance to apoptosis. Further investigation revealed that increasing MMP-10 expression stimulates the expression of HIF-1α and MMP-2 (pro-angiogenic factors) and PAI-1 and CXCR2 (pro-metastatic factors), and accordingly, targeting MMP-10 with siRNA in vivo resulted in diminution of xenograft tumor growth with a concomitant reduction of angiogenesis and a stimulation of apoptosis.

Conclusion: Taken together, our findings show that MMP-10 can play a significant role in tumor growth and progression, and that MMP-10 perturbation may represent a rational strategy for cancer treatment.

Keywords: Angiogenesis, Apoptosis, Cancer, Invasion, MMP-10

Reference

Zhang G, Miyake M, Lawton A, Goodison S,  Rosser CJ. Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors. BMC Cancer. 2014, 14:310. 

Results and findings

MMP-10 is the important factor to promote tumor growth and progression through enhanced tumor cell migration and invasion, angiogenesis, and apoptosis resistance. Interestingly, MMP-10 may be a new molecular target for cancer therapy.

Citations

1. Zhang et al. (2014) reported that both MMP-10 activities in vivo and in vitro experiments were shown to be important role in the tumor growth through upregulated key molecules related to angiogenesis, metastasis, and apoptosis resistance.

2. Zhang et al. (2014) revealed that MMP-10 with siRNA could decrease tumor growth in vivo experiment that is associated with a reduction of angiogenesis and a stimulation of apoptosis.