title: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.forename: Adrienne
authors.initials: A
authors.lastname: Lawton
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando Health, Orlando, FL 32827, USA. crosser@cc.hawaii.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034741:RNA, Small Interfering; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; D053506:Matrix Metalloproteinase 10