A function-blocking CD47 antibody suppresses stem cell and EGF signaling in triple-negative breast cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• CD47 is a receptor involved in immune evasion and cancer stem cell (CSC) self-renewal.
• Elevated CD47 expression on cancer cells inhibits macrophage phagocytosis via SIRPα signaling.
• Anti-CD47 antibodies are being investigated for cancer therapy, potentially targeting CSCs.

Purpose of the Study:

• To investigate the therapeutic potential of anti-CD47 antibody B6H12 against breast cancer stem cells (CSCs).
• To elucidate the mechanism of action of B6H12 in CSCs, focusing on SIRPα-independent pathways.
• To assess the impact of B6H12 on CSC proliferation, differentiation, and key gene expression.

Main Methods:

• Treatment of breast CSC lines (MDA-MB-231, T47D) with anti-CD47 antibody B6H12.
• Assessment of cell proliferation and asymmetric cell division.
• Gene expression analysis (EGFR, KLF4) and microRNA-7 levels.
• Inhibition of EGF-induced EGFR tyrosine phosphorylation.

Main Results:

• B6H12 treatment decreased proliferation and asymmetric cell division in MDA-MB-231 and T47D CSCs.
• B6H12 treatment reduced EGFR and KLF4 expression and increased microRNA-7 expression in CSCs.
• B6H12 inhibited EGF-induced EGFR phosphorylation, suggesting a direct effect on signaling.
• Gene expression changes correlated with CD47 mRNA in human breast cancers, indicating in vivo relevance.

Conclusions:

• Anti-CD47 antibody B6H12 can inhibit CSC proliferation and promote differentiation through a SIRPα-independent mechanism.
• B6H12 impacts CSCs by downregulating EGFR and KLF4 via enhanced microRNA-7 activity.
• This study reveals a novel therapeutic strategy targeting CSCs by inducing their differentiation.