Inhibition of dendritic cell migration by transforming growth factor-1 increases tumor-draining lymph node metastasis

Background: transforming growth factor (tgf)- is known to be produced by progressor tumors and to immobilize dendritic cells (dcs) within those tumors. moreover,although tgf-1 has been shown to promote tumor progression,there is still no direct,in vivo evidence as to whether tgf-1 is able to directly induce distant metastasis. methods. to address that issue and investigate the mechanism by which tgf-1 suppresses dc activity,we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing tgf-1 or empty vector (mock). results: the numbers of dcs within lymph nodes draining the resultant tgf-1-expressing tumors was significantly lower than within nodes draining tumors not expressing tgf-1. 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-1-expressing tumors than within nodes draining tumors not expressing tgf-1. in addition,14 days after tumor cell inoculation,lymph node metastasis occurred more frequently in mice inoculated with tgf-1 transfectants than in those inoculated with the mock transfectants. conclusions: these findings provide new evidence that tumor-derived tgf-1 inhibits migration of dcs from tumors to their draining lymph nodes,and this immunosuppressive effect of tgf-1 increases the likelihood of metastasis in the affected nodes. © 2012 imai et al.; licensee biomed central ltd.