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

ABSTRACT: 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.

SUBMITTER: Imai K 

PROVIDER: S-EPMC3298529 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature