title: Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis.
abstract: BACKGROUND
  Transforming growth factor (TGF)-β is known to be produced by progressor tumors and to immobilize dendritic cells (DCs) within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct, in vivo evidence as to whether TGF-β1 is able to directly induce distant metastasis.
  
  
  METHODS
  To address that issue and investigate the mechanism by which TGF-β1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock).
  
  
  RESULTS
  The numbers of DCs within lymph nodes draining the resultant TGF-β1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-β1. We then injected fluorescently labeled bone marrow-derived dendritic cells into the tumors, and subsequent analysis confirmed that the tumors were the source of the DCs within the tumor-draining lymph nodes, and that there were significantly fewer immature DCs within the nodes draining TGF-β1-expressing tumors than within nodes draining tumors not expressing TGF-β1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-β1 transfectants than in those inoculated with the mock transfectants.
  
  
  CONCLUSIONS
  These findings provide new evidence that tumor-derived TGF-β1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-β1 increases the likelihood of metastasis in the affected nodes.
authors.affiliation: Department of Chest, Breast and Endocrinologic Surgery, Akita University Graduate School of Medicine, Japan. ka10hiro3@biglobe.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
authors.forename: Souichi
authors.initials: S
authors.lastname: Koyota
authors.forename: Manabu
authors.initials: M
authors.lastname: Ito
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005822:Genetic Vectors; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D016212:Transforming Growth Factor beta