Antibodies toward Na⁺,HCO₃^--cotransporter NBCn1/SLC4A7 block net acid extrusion and cause pH-dependent growth inhibition and apoptosis in breast cancer.

ABSTRACT:

Background

Na⁺,HCO₃^--cotransporter NBCn1/Slc4a7 accelerates murine breast carcinogenesis. Lack of specific pharmacological tools previously restricted therapeutic targeting of NBCn1 and identification of NBCn1-dependent functions in human breast cancer.

Methods

We develop extracellularly-targeted anti-NBCn1 antibodies, screen for functional activity on cells, and evaluate (a) mechanisms of intracellular pH regulation in human primary breast carcinomas, (b) proliferation, cell death, and tumor growth consequences of NBCn1 in triple-negative breast cancer, and (c) association of NBCn1-mediated Na⁺,HCO₃^--cotransport with human breast cancer metastasis.

Results

We identify high-affinity (K_D ≈ 0.1

SUBMITTER: Axelsen TV 

PROVIDER: S-EPMC10991555 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature