| First Author | Borczuk AC | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 21 | Pages | 6665-75 |
| PubMed ID | 21911454 | Mgi Jnum | J:177379 |
| Mgi Id | MGI:5294875 | Doi | 10.1158/0008-5472.CAN-11-1590 |
| Citation | Borczuk AC, et al. (2011) Progression of Human Bronchioloalveolar Carcinoma to Invasive Adenocarcinoma Is Modeled in a Transgenic Mouse Model of K-ras-Induced Lung Cancer by Loss of the TGF-beta Type II Receptor. Cancer Res 71(21):6665-75 |
| abstractText | Clinical investigations have suggested that repression of the TGF-beta type II receptor (TbetaRII) may be an important step in progression of lung adenocarcinoma from an indolent in situ state to a frank invasive carcinoma. To test this hypothesis, we compared the effects of deleting the murine homolog of this receptor (Tgfbr2) in a mouse model of mutant K-ras-induced lung carcinoma, which normally induces the formation of multifocal tumors of low invasive potential. In this model, loss of Tgfbr2 induced a highly invasive phenotype associated with lymph node metastasis and reduced survival. Tumor-associated stromal cells displayed an immunosuppressive profile marked by increased numbers of B and T cells. Moreover, tumor stromal cell profiling revealed a developmental TGF-beta response profile that associated with a collagenized extracellular matrix and increased invasion of TGF-beta nonresponsive tumor cells. Together, these results suggest that our KrasTgfbr2(-/-) mouse model of invasive lung carcinoma mirrors the genomic response and clinical progression of human lung adenocarcinoma, recapitulating changes in lung stromal pathways that occur in the tumor microenvironment during malignant progression in this disease. Cancer Res; 71(21); 6665-75. (c)2011 AACR. |
