title: Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing mice.
abstract: BACKGROUND
  Metastasis via the lymphatic system is promoted by lymphangiogenesis. Alterations of the lymphatic channels during the progression of metastasis to regional lymph nodes (LNs) remain unexplored. To examine whether tumor-induced LN lymphangiogenesis controls metastasis to regional LNs, we investigated cervical LN metastasis in a mouse model of oral melanoma.
  
  
  METHODS
  Injection of B16F10 melanoma cells into mouse tongues replicated spontaneous cervical LN metastasis. We performed histological, immunofluorescent, and histomorphometric analyses of tumor-reactive lymphadenopathy and lymphangiogenesis in tumor-associated LNs. We investigated the expression of vascular endothelial growth factor (VEGF)-C and its receptor, VEGF receptor-3 (VEGFR-3), in tumor cells and tissues, and LNs by reverse transcription polymerase chain reaction and immunofluorescence.
  
  
  RESULTS
  Tumor-associated LNs comprised sentinel LNs (SLNs) before and after tumor cell invasion (tumor-bearing SLNs), and LNs adjacent or contralateral to tumor-bearing SLNs. Extensive lymphangiogenesis appeared in SLNs before evidence of metastasis. After metastasis was established in SLNs, both LNs adjacent and contralateral to tumor-bearing SLNs demonstrated lymphangiogenesis. Interaction between VEGF-C-positive melanoma cells and VEGFR-3-positive lymphatic vessels was evident in tumor-associated LNs.
  
  
  CONCLUSIONS
  LN lymphangiogenesis contributes a progression of tumor metastasis from SLNs to other regional LNs.
authors.affiliation: Department of Morphological Biology, Division of Pathology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
authors.forename: Ryuki
authors.initials: R
authors.lastname: Ozasa
authors.forename: Jun
authors.initials: J
authors.lastname: Ohno
authors.forename: Teruaki
authors.initials: T
authors.lastname: Iwahashi
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental; D051379:Mice; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3