| First Author | Ostapoff KT | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 18 | Pages | 4996-5007 |
| PubMed ID | 25060520 | Mgi Jnum | J:215991 |
| Mgi Id | MGI:5607465 | Doi | 10.1158/0008-5472.CAN-13-1807 |
| Citation | Ostapoff KT, et al. (2014) Neutralizing murine TGFbetaR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis. Cancer Res 74(18):4996-5007 |
| abstractText | Elevated levels of TGFbeta are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFbeta pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFbeta remains challenging because TGFbeta has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization of TGFbeta promotes tumor progression of genetic murine models of pancreatic cancer. Here, we report that neutralizing the activity of murine TGFbeta receptor 2 using a monoclonal antibody (2G8) has potent antimetastatic activity in orthotopic human tumor xenografts, syngeneic tumors, and a genetic model of pancreatic cancer. 2G8 reduced activated fibroblasts, collagen deposition, microvessel density, and vascular function. These stromal-specific changes resulted in tumor cell epithelial differentiation and a potent reduction in metastases. We conclude that TGFbeta signaling within stromal cells participates directly in tumor cell phenotype and pancreatic cancer progression. Thus, strategies that inhibit TGFbeta-dependent effector functions of stromal cells could be efficacious for the therapy of pancreatic tumors. Cancer Res; 74(18); 4996-5007. (c)2014 AACR. |
