%0 Journal Article
%T Inhibition of dendritic cell migration by transforming growth factor-¦Â1 increases tumor-draining lymph node metastasis
%A Kazuhiro Imai
%A Yoshihiro Minamiya
%A Souichi Koyota
%A Manabu Ito
%A Hajime Saito
%A Yusuke Sato
%A Satoru Motoyama
%A Toshihiro Sugiyama
%A Jun-ichi Ogawa
%J Journal of Experimental & Clinical Cancer Research
%D 2012
%I BioMed Central
%R 10.1186/1756-9966-31-3
%X To address that issue and investigate the mechanism by which TGF-¦Â1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-¦Â1 or empty vector (mock).The numbers of DCs within lymph nodes draining the resultant TGF-¦Â1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-¦Â1. 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-¦Â1-expressing tumors than within nodes draining tumors not expressing TGF-¦Â1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-¦Â1 transfectants than in those inoculated with the mock transfectants.These findings provide new evidence that tumor-derived TGF-¦Â1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-¦Â1 increases the likelihood of metastasis in the affected nodes.Transforming growth factor (TGF) -¦Â can reportedly promote cancer metastasis by affecting the tumor microenvironment in a manner that facilitates tumor cell invasion [1,2] and by inhibiting immune cell function [3]. Consistent with those reports, overproduction of TGF-¦Â by tumors is frequently associated with metastasis [4-6] and a poor prognosis in patients with cancer [7-10]. Among the three highly homologous TGF-¦Â isoforms, TGF-¦Â1 is the most abundant and most extensively studied [11]. We previously showed that tumor-derived TGF-¦Â1 causes a reduction in the number of dendritic cells (DCs) within tumor-draining lymph nodes (TDLNs) [12]. It also has been shown that TGF-¦Â1 is produced by progressor tumors and that it immobilizes the DCs within those tumors [13]. This is noteworthy because DCs are highly speci
%K dendritic cell
%K migration
%K transforming growth factor-¦Â1
%K tumor draining lymph node
%K lymph node metastasis
%U http://www.jeccr.com/content/31/1/3