| First Author | Cho HC | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 23 | Pages | 7250-8 |
| PubMed ID | 22088965 | Mgi Jnum | J:178608 |
| Mgi Id | MGI:5299361 | Doi | 10.1158/0008-5472.CAN-11-0903 |
| Citation | Cho HC, et al. (2011) Identification of Tumorigenic Cells in KrasG12D-Induced Lung Adenocarcinoma. Cancer Res 71(23):7250-8 |
| abstractText | We established an inducible Kras(G12D)-driven lung adenocarcinoma in CCSP-rtTA/TetO-Cre/LSL-Kras(G12D) mice that enable pursuits of the cellular and molecular processes involved in Kras-induced tumorigenesis. To investigate the cellular origin of this cancer, we first report a strategy using fluorescence-activated cell sorting fractionation that could highly enrich bronchiolar Clara and alveolar type II cells, respectively. The EpCAM(+)MHCII(-) cells (bronchiolar origin) were more enriched with tumorigenic cells in generating secondary tumors than EpCAM(+)MHCII(+) cells (alveolar origin) in primary tumors that had been already initiated with oncogenic Kras activation. In addition, secondary tumors derived from EpCAM(+)MHCII(-) cells showed diversity of tumor locations compared with those derived from EpCAM(+)MHCII(+) cells. In the alveolar region, secondary tumors from EpCAM(+)MHCII(-) cells expressed not only bronchiolar epithelial marker, panCK, but also differentiation marker, proSPC, consistent with the notion that cancer-initiating cells display not only the abilities for self-renewal but also the features of differentiation to generate heterogeneous tumors with phenotypic diversity. Furthermore, high level of ERK1/2 activation and colony-forming ability as well as lack of Sprouty-2 expression were also observed in EpCAM(+)MHCII(-) cells. Therefore, these results suggest that bronchiolar Clara cells are the origin of cells and tumorigenesis for Kras(G12D)-induced neoplasia in the lungs. Cancer Res; 71(23); 7250-8. (c)2011 AACR. |
