STAT1 gene deficient mice develop accelerated breast cancer growth and metastasis which is reduced by IL-17 blockade

Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K. Ahirwar, Pablo C. Alarcon, Rachel H. Sperling, Ellen Moretti, Marissa S. Pioso, Jennifer Kimble, Mohd W. Nasser, Ramesh K. Ganju, Cesar Terrazas, Abhay R. Satoskar

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1−/− mice orthotopically implanted with metastatic 4T1.2 cells. Primary tumor development was faster in STAT1−/− mice and these mice developed significantly bigger primary tumors and displayed more lung metastasis compared with WT counterparts. STAT1−/− mice showed elevated Ly6G+CD11b+ granulocytic MDSC infiltration in their primary tumors and spleens with concomitant upregulation of Mmp9 and Cxcl1 expression in tumors compared with WT counterparts. Blockade of IL-17A in primary tumor-bearing STAT1−/− mice suppressed accumulation of Ly6G+CD11b+ cells and markedly reduced lung metastasis. These data show that STAT1 is an important suppressor of primary breast tumor growth and metastasis. Importantly, we found anti-IL-17 treatment can rescue STAT1 deficient animals from developing exacerbated metastasis to the lungs which could be important for immunotherapies for immunocompromised breast cancer patients.

Original languageEnglish (US)
Article numbere1361088
JournalOncoImmunology
Volume6
Issue number11
DOIs
StatePublished - Nov 2 2017

Keywords

  • IL-17
  • breast cancer
  • metastasis
  • neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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