title: MMP13 Regulates Aggressiveness of Pediatric Multiple Myeloma Through VEGF-C.
abstract: OBJECTIVE
  Even though the blood and lymphatic vascular systems are both involved in the occurrence of cancer metastases, it is believed that lymphatic system is primarily responsible for the initial metastasis. Nevertheless, the molecular mechanisms underlying lymphangiogenesis of multiple myeloma (MM), especially in pediatric period, have not been clarified.
  
  
  METHODS
  Here we studied vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 13 (MMP13) in pediatric MM patients. We overexpressed or inhibited VEGF-C in MM cells to study their effects on MMP13, and vice versa. A specific inhibitor for PI3k/Akt signaling pathway was used to examine the role of PI3k/Akt signaling in this regulatory axis.
  
  
  RESULTS
  Both VEGF-C and MMP13 significantly upregulated in MM with lymph-node metastases. A strong correlation between VEGF-C and MMP13 were detected in MM specimen. Using a human MM line 8226, we found that VEGF-C was regulated by MMP13 in MM cells, but not vice versa. Moreover, a specific PI3k/Akt inhibitor significantly abolished the effect of MMP13 on VEGF-C activation.
  
  
  CONCLUSIONS
  Since VEGF-C is a well-known growth factor for lymphatic vessels, our data suggest that MMP13 may activate VEGF-C to promote cancer cell metastasis through lymphatic vascular systems in pediatric MM.
authors.affiliation: Department of Pediatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Xu
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Yanming
authors.initials: Y
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D042582:Vascular Endothelial Growth Factor C; D019869:Phosphatidylinositol 3-Kinases; D053509:Matrix Metalloproteinase 13