isolation-culturing-primary-murine-adipocytes-from-lean-obese

Isolation and Culturing of Primary Murine Adipocytes from Lean and Obese Mice

Adipose tissue is primarily composed of mature, lipid-laden adipocytes by volume. These postmitotic cells play a critical role in energy storage and ...

University of Utah School of Medicine

Obesity is a predisposition factor for breast cancer, suggesting a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of ten human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells (ASPC). The screen identified a key adipogenic modulator, Zinc Alpha-2-Glycoprotein (ZAG/AZGP1), secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG in TNBC patients, but not other clinical subtypes of breast cancer, is linked to poor prognosis. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of ASPCs into cancer-associated fibroblasts to support tumorigenesis.

Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis.

Obesity is a modifiable predisposition factor for postmenopausal breast cancer. This suggests a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of 10 human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells. The screen identified an adipogenic modulator, zinc-alpha-2-glycoprotein (ZAG/AZGP1) that is secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG is linked to poor prognosis in patients with TNBC but not in patients with other clinical subtypes of breast cancer. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of adipocyte stem and progenitor cells into cancer-associated fibroblasts to support tumorigenesis.

Article	Year
Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis. bioRxiv : the preprint server for biology\| PubMed ID: 38496643	2024
Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis. Cancer research communications\| PubMed ID: 38888911	2024

Meghan C. Curtin

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