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Updated: Jun 23, 2025
06:35
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
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Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis
Surbhi Verma1, Stephanie D Giagnocavo1, Meghan C Curtin1
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah.
Cancer Research Communications
|June 18, 2024
Summary
Triple-negative breast cancer cells secrete zinc-alpha-2-glycoprotein (ZAG), which promotes adipose tissue fibrosis and inhibits adipogenesis. ZAG depletion reduces tumor growth and is linked to poor prognosis in TNBC patients.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Obesity is a risk factor for postmenopausal breast cancer, suggesting interactions between cancer cells and adipose tissue.
- Breast cancer cells can alter the composition and function of the mammary white adipose tissue microenvironment.
Purpose of the Study:
- To investigate how breast cancer cells modify adipose tissue.
- To identify specific factors secreted by breast cancer cells that influence adipocyte stem and progenitor cells.
Main Methods:
- Screening of secretomes from 10 human breast cancer cell lines.
- Assessing the modulation of adipocyte stem and progenitor cell differentiation.
- Depletion of identified factors in cancer cells to evaluate effects on fibrosis and tumor growth.
Main Results:
- Zinc-alpha-2-glycoprotein (ZAG) was identified as an adipogenic modulator secreted by triple-negative breast cancer (TNBC) cells.
- TNBC-secreted ZAG inhibits adipogenesis and induces fibrotic gene expression.
- ZAG depletion in TNBC cells attenuated adipose tissue fibrosis and inhibited tumor growth.
- High ZAG expression correlated with poor prognosis in TNBC patients.
Conclusions:
- TNBC-secreted ZAG promotes the transdifferentiation of adipocyte stem and progenitor cells into cancer-associated fibroblasts.
- This process supports tumorigenesis by altering the adipose tissue microenvironment.
- ZAG is a potential therapeutic target for TNBC.
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