FZD7 expression marks mammary tumor-initiating cells

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• The WNT signaling pathway is crucial in tumorigenesis, particularly in breast cancer.
• Identifying specific WNT pathway components driving tumor development is challenging due to pathway complexity.

Purpose of the Study:

• To identify key WNT pathway components driving mammary tumor development in a genetically engineered mouse model.
• To evaluate the therapeutic potential of targeting identified components in breast cancer.

Main Methods:

• Utilized the MMTV-Wnt1 genetically engineered mouse model for mixed-lineage mammary tumors.
• Assessed tumor cell tumorigenic potential using orthotopic transplantation and tumor organoid assays.
• Administered Fzd7-specific antibody-drug conjugates to evaluate therapeutic efficacy.

Main Results:

• Frizzled class receptor 7 (Fzd7) was identified as a key player in MMTV-Wnt1-induced mammary tumors.
• Fzd7-expressing cells exhibited enhanced tumorigenic potential.
• Fzd7-specific antibody-drug conjugate treatment significantly suppressed tumor growth, irrespective of tumor heterogeneity.

Conclusions:

• Fzd7 marks a population of putative tumor-initiating cells within MMTV-Wnt1 mammary tumors.
• Targeting Fzd7 represents a promising therapeutic strategy for breast cancer, potentially effective against triple-negative subtypes.