Gene expression profile of breast cancer cell lines

ABSTRACT: Inflammatory Breast Cancer (IBC) is the most aggressive form of breast cancer, but understanding of the unique aspects of IBC biology lags far behind that of other breast cancers. One of the key barriers in advancing understanding of the molecular determinants of IBC has been the lack of adequate models for this disease that presents with distinct clinical and histopathological features. We describe here a novel human triple-negative IBC cell line, A3250, that recapitulates key features of human IBC in a mouse orthotopic model including skin erythema, diffuse tumor growth, high stroma to tumor ratio, dermal lymphatic invasion, and extensive lymph node and distant metastases. Tumor-associated macrophages were particularly enriched, and A3250 cells expressed very high levels of CCL2, a macrophage recruiting chemokine in the absence of detectable levels of its cognate receptor. CCL2 knockdown led to a striking reduction in macrophage densities, tumor cell proliferation, and metastasis in vivo. These results identify tumor-derived CCL2 as a key factor driving macrophage expansion and indirectly, the growth of A3250 IBC cells in vivo. Comparison of the A3250 chemokine expression profile with human IBC expression data sets revealed sharing of this profile across different IBC subtypes as well as enrichment for macrophage expression. Thus, this human IBC model provides a unique opportunity to uncover novel aspects of IBC biology, and to test novel therapies for this deadly disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159987 | GEO | 2023/09/30

REPOSITORIES: GEO