| First Author | Castiello L | Year | 2018 |
| Journal | Cancer Immunol Res | Volume | 6 |
| Issue | 6 | Pages | 658-670 |
| PubMed ID | 29622580 | Mgi Jnum | J:326020 |
| Mgi Id | MGI:7294320 | Doi | 10.1158/2326-6066.CIR-17-0675 |
| Citation | Castiello L, et al. (2018) Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells. Cancer Immunol Res 6(6):658-670 |
| abstractText | Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages of tumor initiation and progression. IFN-I acts directly on tumor cells to inhibit cell growth and indirectly by activating immune cells to mount antitumor responses. To understand the role of endogenous IFN-I in spontaneous, oncogene-driven carcinogenesis, we characterized tumors arising in HER2/neu transgenic (neuT) mice carrying a nonfunctional mutation in the IFNI receptor (IFNAR1). Such mice are unresponsive to this family of cytokines. Compared with parental neu(+/-) mice (neuT mice), IFNAR1(-/-) neu(+/-) mice (IFNAR-neuT mice) showed earlier onset and increased tumor multiplicity with marked vascularization. IFNAR-neuT tumors exhibited deregulation of genes having adverse prognostic value in breast cancer patients, including the breast cancer stem cell (BCSC) marker aldehyde dehydrogenase-1A1 (ALDH1A1). An increased number of BCSCs were observed in IFNAR-neuT tumors, as assessed by ALDH1A1 enzymatic activity, clonogenic assay, and tumorigenic capacity. In vitro exposure of neuT(+) mammospheres and cell lines to antibodies to IFN-I resulted in increased frequency of ALDH(+) cells, suggesting that IFN-I controls stemness in tumor cells. Altogether, these results reveal a role of IFN-I in neuT-driven spontaneous carcinogenesis through intrinsic control of BCSCs. Cancer Immunol Res; 6(6); 658-70. (c)2018 AACR. |
