| First Author | Li Z | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 21 | Pages | 8687-94 |
| PubMed ID | 18974110 | Mgi Jnum | J:140641 |
| Mgi Id | MGI:3814256 | Doi | 10.1158/0008-5472.CAN-08-0449 |
| Citation | Li Z, et al. (2008) Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis. Cancer Res 68(21):8687-94 |
| abstractText | The increase of interleukin-4 (IL-4) level in tumor environment and the up-regulation of IL-4 receptor (IL-4R) on tumor cells have been long observed. However, their significance for tumor development has not been investigated. Here, we found that endogenous IL-4 promotes tumor growth because neutralizing IL-4 by 11B11 monoclonal antibody (mAb) significantly delayed the growth of MCA205 fibrosarcoma. We also observed that tumor cells with higher IL-4R expression have more chances to survive in immunocompetent mice. To investigate how endogenous IL-4 influences tumor growth, we established a pair of tumor cells with or without IL-4R expression from the common parental cells. IL-4R-competent tumors exhibit increased growth compared with its IL-4R-deficient counterparts when inoculated into syngeneic mice. This growth advantage was still kept in IL-4R knockout mice but was abrogated in mice given i.p. with IL-4 neutralizing mAb. In vitro analyses indicate that IL-4 neither affects the proliferation of tumor cells nor changes the expression of several immune-related molecules, such as MHC-I, Fas, and B7-H3. Nonetheless, IL-4 up-regulates antiapoptotic gene expression in tumor cells and reduces apoptosis of tumor cells in vivo, as evidenced by real-time PCR, immunoblotting, and TUNEL staining. These findings were helpful to understand the long clinical observation and revealed that endogenous IL-4, the product of host immune response, can be used by tumor cells to facilitate their growth. |
