Here we provide new direct evidence for such an effect. In the present study we did not directly prove that the
reduction in DCs migration causes tumor metastasis into TDLNs. In addition to its immunosuppressive effect, TGF-β1 upregulates https://www.selleckchem.com/products/a-1155463.html cell motility and invasiveness, as well as epithelial-to-mesenchymal transition . These effects may have also promoted lymph node metastasis in our study. Further investigation will be needed to more precisely define the role of tumor-derived TGF-β1 in tumor lymph node metastasis. Conclusions In sum, we have shown that overexpression of TGF-β1 by tumor cells promotes tumor metastasis into TDLNs, most likely by inhibiting DC migration from tumors towards TDLNs. This immunosuppressive effect would be expected to promote lymph node metastasis in patients with malignant disease. References 1. Giampieri S, Pinner S, Sahai E: Intravital imaging illuminates transforming growth factor beta signaling switches during metastasis. Cancer Res 2010, 70:3435–3439.PubMedCrossRef 2. Korpal M, Kang Y: Targeting the transforming growth factor-beta signaling pathway in metastatic cancer. Eur J Cancer 2010, 46:1232–1240.PubMedCrossRef 3. Teicher BA: Transforming growth factor-beta and the immune response to malignant disease. Clin Cancer Res 2007, 13:6247–6251.PubMedCrossRef
4. Leivonen SK, Kähäri VM: Transforming growth factor-beta signaling in cancer invasion and metastasis. Int J Cancer 2007, 121:2119–2124.PubMedCrossRef 5. Han G, Lu SL, Li AG, He W, Corless CL, Kulesz-Martin M, Wang XJ: Distinct mechanisms of TGF-beta1-mediated Glutathione peroxidase selleck screening library epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis. J Clin Invest 2005,
115:1714–1723.PubMedCrossRef 6. Angenete E, Langenskiöld M, Palmgren I, Falk P, Oresland T, Ivarsson ML: Transforming growth factor beta-1 in rectal Tipifarnib tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients. Int J Colorectal Dis 2007, 22:1331–1338.PubMedCrossRef 7. Wikström P, Stattin P, Franck-Lissbrant I, Damber JE, Bergh A: Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate 1998, 37:19–29.PubMedCrossRef 8. Hasegawa Y, Takanashi S, Kanehira Y, Tsushima T, Imai T, Okumura K: Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer 2001, 91:964–971.PubMedCrossRef 9. Saito H, Tsujitani S, Oka S, Kondo A, Ikeguchi M, Maeta M, Kaibara N: The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma. Cancer 1999, 86:1455–1462.PubMedCrossRef 10.