| First Author | Schmid MC | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 22 | Pages | 6965-75 |
| PubMed ID | 21948958 | Mgi Jnum | J:178009 |
| Mgi Id | MGI:5297004 | Doi | 10.1158/0008-5472.CAN-11-0588 |
| Citation | Schmid MC, et al. (2011) Combined Blockade of Integrin-alpha4beta1 Plus Cytokines SDF-1alpha or IL-1beta Potently Inhibits Tumor Inflammation and Growth. Cancer Res 71(22):6965-75 |
| abstractText | Tumor-associated macrophages promote tumor growth by stimulating angiogenesis and suppressing antitumor immunity. Thus, therapeutics that inhibit macrophage recruitment to tumors may provide new avenues for cancer therapy. In this study, we showed how chemoattractants stromal cell-derived growth factor 1 alpha (SDF-1alpha) and interleukin 1 beta (IL-1beta) collaborate with myeloid cell integrin-alpha4beta1 to promote tumor inflammation and growth. We found that SDF-1alpha and IL-1beta are highly expressed in the microenvironments of murine lung, pancreatic, and breast tumors; surprisingly, SDF-1alpha was expressed only by tumor cells, whereas IL-1beta was produced only by tumor-derived granulocytes and macrophages. In vivo, both factors directly recruited proangiogenic macrophages to tissues, whereas antagonists of both factors suppressed tumor inflammation, angiogenesis, and growth. Signals induced by IL-1beta and SDF-1alpha promoted the interaction of talin and paxillin with the cytoplasmic tails of integrin-alpha4beta1, thereby stimulating myeloid cell adhesion to endothelium in vitro and in vivo. Inhibition of integrin-alpha4beta1, SDF-1alpha, or IL-1beta was sufficient to block tumor inflammation and growth, and the combined blockade of these molecules greatly accentuated these effects. Furthermore, antagonists of integrin-alpha4beta1 inhibited chemotherapy-induced tumor inflammation and acted synergistically with chemotherapeutic agents to suppress tumor inflammation and growth. These results show that targeting myeloid cell recruitment mechanisms can be an effective approach to suppress tumor progression. Cancer Res; 71(22): 6965-75. (c)2011 AACR. |
