| First Author | Ichise T | Year | 2010 |
| Journal | Cell Struct Funct | Volume | 35 |
| Issue | 1 | Pages | 3-13 |
| PubMed ID | 20190463 | Mgi Jnum | J:260662 |
| Mgi Id | MGI:6152541 | Doi | 10.1247/csf.09025 |
| Citation | Ichise T, et al. (2010) Humanized gene replacement in mice reveals the contribution of cancer stroma-derived HB-EGF to tumor growth. Cell Struct Funct 35(1):3-13 |
| abstractText | Tumor progression is a complex process that involves the interaction of cancer cells with the cancer-surrounding stromal cells. The cancer stroma influences the cancer cell growth and metastatic potential. The EGF family growth factor HB-EGF is synthesized in cancer cells and plays pivotal roles in oncogenic transformation and tumor progression, but the contribution of HB-EGF expressed in tumor stromal cells to tumor growth remains unclear. In the present study, we found that HB-EGF was expressed in host-derived cancer stromal cells in xenograft and allograft mouse tumor models. CRM197 is a specific inhibitor of human HB-EGF that has no effect on mouse HB-EGF. To elucidate whether host-derived stromal HB-EGF contributes to tumor growth, we generated knock-in mice expressing a CRM197-inhibitable humanized mutant form of HB-EGF. Administration of CRM197 to humanized knock-in mice that were bearing tumors derived from human or mouse cancer cells revealed that inhibition of host-derived stromal HB-EGF by CRM197 significantly reduced tumor growth. These results suggest that HB-EGF in the cancer-associated stroma plays a significant role for tumor growth, and that the HB-EGF derived from the stroma, as well as that expressed by cancer cells, is a potential target for cancer therapy. The present results also suggest that the humanized HB-EGF knock-in mice could be utilized for pathophysiological studies of HB-EGF as well as the development of therapeutic strategies targeting HB-EGF. |
