title: Vascular endothelial growth factor-C secreted by pancreatic cancer cell line promotes lymphatic endothelial cell migration in an in vitro model of tumor lymphangiogenesis.
abstract: OBJECTIVE
  To investigate mechanisms underlying lymphatic node metastasis in pancreatic cancer, we examined roles of vascular endothelial growth factor-C (VEGF-C) in tumor lymphangiogenesis.
  
  
  METHODS
  We measured VEGF-C secretion by pancreatic cancer cell lines using enzyme-linked immunosorbent assay and examined effects of different cell lines on lymphatic endothelial cells (LECs) in vitro.
  
  
  RESULTS
  We identified VEGF-C high-secretion (MIA PaCa-2) and low-secretion cell lines (BxPC-3). The trend of enhancement of LEC proliferation by recombinant human VEGF-C (rVEGF-C) was not statistically significant. Numbers of migrating cells were increased by rVEGF-C treatment in a dose-dependent manner. The MIA PaCa-2 cell culture supernatant caused greater LEC migration than the BxPC-3 supernatant. The VEGF-C effects were significantly inhibited by rVEGF receptor 3 (rVEGF R3)/Fc chimera. In LEC/fibroblast coculture on collagen gel, LEC capillary formation was significantly enhanced by coculture with MIA PaCa-2 cells compared with BxPC-3 cells. Enhanced capillary formation with MIA PaCa-2 cells was inhibited by rVEGF R3/Fc chimera, implying VEGF-C involvement in progression of LEC sprouting in a tumor microenvironment.
  
  
  CONCLUSIONS
  Because VEGF-C secreted by pancreatic cancer cells plays an important role in LEC migration in pancreatic cancer lymphangiogenesis, it is possible that rVEGF R3/Fc chimera might have a role in controlling lymph node metastasis.
authors: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Japan. nochi@med.nagoya-cu.ac.jp
authors: Nobuo
authors: N
authors: Ochi
authors: Yoichi
authors: Y
authors: Matsuo
authors: Hirozumi
authors: H
authors: Sawai
authors: Akira
authors: A
authors: Yasuda
authors: Hiroki
authors: H
authors: Takahashi
authors: Mikinori
authors: M
authors: Sato
authors: Hitoshi
authors: H
authors: Funahashi
authors: Yuji
authors: Y
authors: Okada
authors: Tadao
authors: T
authors: Manabe
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3