The role for endogenous type I Interferon in the metabolic reprogramming of spontaneous mammary tumors in HER2/neu transgenic mice Our study aims to identify, by in vivo MRS and ex vivo high resolution (HR)-MRS, the metabolic changes involved in spontaneous carcinogenesis occurring in Her2/neu transgenic mice, with particular focus on the role of endogenous type I IFN (IFN-I). Our group reported that the lack of endogenous IFN-I system significantly affects Her2/neu carcinogenesis. Since this phenomenon was not related to the known immunomodulatory properties of these cytokines, we investigated whether the possible reshaping of metabolic pathways was involved. Both in vivo MRS and ex vivo high resolution (HR)-MRS revealed that nontumoral mammary glands of mice lacking a functional endogenous IFN-I (IFNARI-/-) had increased fatty acids concentration with respect to the wild type counterpart. This result paralleled the observation of specific trascriptomic profiles in IFNARI-/- normal mammary glands, that exhibited decreased expression of genes involved in mitochondrial activity and increased expression of Sterol regulatory element-binding proteins, a known regulator of fatty acids biosynthesis and an independent prognostic marker in breast cancer. HR-MRS analyses of aqueous metabolites revealed that the metabolic fingerprint of Her2+ tumors lesions was significantly different from normal mammary glands in both IFNARI+/+ and IFNARI-/- mice. The concentration of myo-inositol and glutathione was significantly reduced in IFNARI-/- tumors, suggesting that endogenous IFN-I may exert its antitumor activity by affecting key metabolic regulators of tumor cells proliferation. Our study provide the first evidence that endogenous IFN-I is involved in metabolic pathways in both normal mammary glands and early phase breast cancer.
The role for endogenous type I Interferon in the metabolic reprogramming of spontaneous mammary tumors in HER2/neu transgenic mice / Canese, Rossella; Iorio, Egidio; Chirico, Mattea; Elena Pisanu, Maria; Singh, Taljinder; Palombelli, Gianmauro; Spadaro, Francesca; Cecchetti, Serena; Maria Pacca, Anna; Spada, Massimo; Macchia, Daniele; Teresa D’Urso, Maria; Castiello, Luciano; Aricò, Eleonora. - (2022). (Intervento presentato al convegno Giornata A_IATRIS: Progetti, Collaborazioni e Servizi 2022 tenutosi a Rome).
The role for endogenous type I Interferon in the metabolic reprogramming of spontaneous mammary tumors in HER2/neu transgenic mice
Taljinder Singh;
2022
Abstract
The role for endogenous type I Interferon in the metabolic reprogramming of spontaneous mammary tumors in HER2/neu transgenic mice Our study aims to identify, by in vivo MRS and ex vivo high resolution (HR)-MRS, the metabolic changes involved in spontaneous carcinogenesis occurring in Her2/neu transgenic mice, with particular focus on the role of endogenous type I IFN (IFN-I). Our group reported that the lack of endogenous IFN-I system significantly affects Her2/neu carcinogenesis. Since this phenomenon was not related to the known immunomodulatory properties of these cytokines, we investigated whether the possible reshaping of metabolic pathways was involved. Both in vivo MRS and ex vivo high resolution (HR)-MRS revealed that nontumoral mammary glands of mice lacking a functional endogenous IFN-I (IFNARI-/-) had increased fatty acids concentration with respect to the wild type counterpart. This result paralleled the observation of specific trascriptomic profiles in IFNARI-/- normal mammary glands, that exhibited decreased expression of genes involved in mitochondrial activity and increased expression of Sterol regulatory element-binding proteins, a known regulator of fatty acids biosynthesis and an independent prognostic marker in breast cancer. HR-MRS analyses of aqueous metabolites revealed that the metabolic fingerprint of Her2+ tumors lesions was significantly different from normal mammary glands in both IFNARI+/+ and IFNARI-/- mice. The concentration of myo-inositol and glutathione was significantly reduced in IFNARI-/- tumors, suggesting that endogenous IFN-I may exert its antitumor activity by affecting key metabolic regulators of tumor cells proliferation. Our study provide the first evidence that endogenous IFN-I is involved in metabolic pathways in both normal mammary glands and early phase breast cancer.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
