Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells

Manoranjan Sahoo; Gajendra K Katara; Mahmood Y Bilal; Safaa A Ibrahim; Arpita Kulshrestha; Sara Fleetwood; Kimiko Suzue; Kenneth D Beaman

doi:10.18632/oncotarget.26061

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Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells

Journal article

Open access

Peer reviewed

Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells

Manoranjan Sahoo, Gajendra K Katara, Mahmood Y Bilal, Safaa A Ibrahim, Arpita Kulshrestha, Sara Fleetwood, Kimiko Suzue and Kenneth D Beaman

Oncotarget, Vol.9(69), pp.33215-33231

09/01/2018

DOI: 10.18632/oncotarget.26061

PMID: 30237863

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Abstract

The interaction of recruited immune effector cells and cancer cells within tumor microenvironment (TME) shapes the fate of cancer progression and metastasis. Many cancers including breast cancer, express a specific vacuolar ATPase (a2V) on their cell surface which acidifies the extracellular milieu helping cancer cell proliferation and metastasis. To understand the role of immune cell-associated-a2V during breast tumor pathogenesis, we knocked-out a2V (KO) from the hematopoietic stem cells (HSC) and generated breast tumors in mice. The a2V-KO mice developed faster growing, larger, and metastatic breast tumors compared to control mice. Further investigation of the TME revealed a significant reduction in the presence of CD4 + and CD8 + T cells in the a2V-KO tumors. Targeted RNA-Seq of the cells of the TME demonstrated that pro-inflammatory cytokines, death receptors, death receptor ligands, and cytotoxic effectors were significantly down-regulated within the a2V-KO TME. Interestingly, analysis of immune cells in the blood, spleen, and thymus of the non-tumor bearing a2V-KO mice revealed a significant decrease in CD4 + and CD8 + T cell populations. For the first time, this study demonstrates that inhibition of V-ATPase expression in HSC leads to a decrease in CD4 + and CD8 + T cell populations and thus promotes breast tumor growth and metastasis.

breast tumor

CD8+ T cells

hematopoietic stem cells (HSC)

Research Paper

tumor microenvironment (TME)

vacuolar ATPase

Details

Title: Subtitle: Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells
Creators: Manoranjan Sahoo - Rosalind Franklin University of Medicine and Science
Gajendra K Katara - Rosalind Franklin University of Medicine and Science
Mahmood Y Bilal - Rosalind Franklin University of Medicine and Science
Safaa A Ibrahim - Rosalind Franklin University of Medicine and Science
Arpita Kulshrestha - Rosalind Franklin University of Medicine and Science
Sara Fleetwood - Rosalind Franklin University of Medicine and Science
Kimiko Suzue - Rosalind Franklin University of Medicine and Science
Kenneth D Beaman - Rosalind Franklin University of Medicine and Science
Resource Type: Journal article
Publication Details: Oncotarget, Vol.9(69), pp.33215-33231
DOI: 10.18632/oncotarget.26061
PMID: 30237863
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Language: English
Date published: 09/01/2018
Academic Unit: Pathology
Record Identifier: 9984185170402771

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