Abstract
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 neumice (neuT mice), IFNAR1/ neumice (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 neuTmmospheres and cell lines to antibodies to IFN-I resulted in increased frequency of ALDHlls, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 658-670 |
| Number of pages | 13 |
| Journal | Cancer immunology research |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2018 |
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ASJC Scopus subject areas
- Immunology
- Cancer Research
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Disruption of IFN-I signaling promotes HER2/Neu tumor progression and breast cancer stem cells. / Castiello, Luciano; Sestili, Paola; Schiavoni, Giovanna; Dattilo, Rosanna; Monque, Domenica M.; Ciaffoni, Fiorella; Iezzi, Manuela; Lamolinara, Alessia; Sistigu, Antonella; Moschella, Federica; Pacca, Anna Maria; Macchia, Daniele; Ferrantini, Maria; Zeuner, Ann; Biffoni, Mauro; Proietti, Enrico; Belardelli, Filippo; Aricò, Eleonora.
In: Cancer immunology research, Vol. 6, No. 6, 01.06.2018, p. 658-670.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Disruption of IFN-I signaling promotes HER2/Neu tumor progression and breast cancer stem cells
AU - Castiello, Luciano
AU - Sestili, Paola
AU - Schiavoni, Giovanna
AU - Dattilo, Rosanna
AU - Monque, Domenica M.
AU - Ciaffoni, Fiorella
AU - Iezzi, Manuela
AU - Lamolinara, Alessia
AU - Sistigu, Antonella
AU - Moschella, Federica
AU - Pacca, Anna Maria
AU - Macchia, Daniele
AU - Ferrantini, Maria
AU - Zeuner, Ann
AU - Biffoni, Mauro
AU - Proietti, Enrico
AU - Belardelli, Filippo
AU - Aricò, Eleonora
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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 neumice (neuT mice), IFNAR1/ neumice (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 neuTmmospheres and cell lines to antibodies to IFN-I resulted in increased frequency of ALDHlls, 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.
AB - 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 neumice (neuT mice), IFNAR1/ neumice (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 neuTmmospheres and cell lines to antibodies to IFN-I resulted in increased frequency of ALDHlls, 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.
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U2 - 10.1158/2326-6066.CIR-17-0675
DO - 10.1158/2326-6066.CIR-17-0675
M3 - Article
AN - SCOPUS:85048293803
VL - 6
SP - 658
EP - 670
JO - Cancer immunology research
JF - Cancer immunology research
SN - 2326-6066
IS - 6
ER -