Microenvironment Modulates Tumorigenicity of Breast Cancer Cells Depending on Hormone Receptor Status

Adipose tissue plays a crucial role in breast cancer (BC) progression by actively modulating the tumor microenvironment. We investigated how tumor proximity modifies adipose tissue by analyzing selected adipose-related and prognosis-associated markers in explants from BC patients and healthy donors. Explants were categorized by proximity to the tumor as <i>adjacent</i> (less than 2 cm), <i>distant</i> (over 2 cm), alongside <i>normal</i> explants (controls). FABP4 and vimentin expression was increased in proximity to the tumor, while caveolin-1, CD44, MMP9, and adiponectin showed minimal or no changes. Conditioned media (CM) from <i>adjacent</i> and <i>normal</i> explants were then assessed for their effects on tumorigenic traits in hormone-receptor-positive breast cancer (HR+ BC) and triple-negative breast cancer (TNBC) cell lines. <i>Adjacent</i>-CM enhanced migration, induced cytoskeletal remodeling, reduced adhesion, and promoted an elongated, motile phenotype in T47D cells. Poor-prognosis markers (caveolin-1, vimentin, CD44) were upregulated in at least one HR+ BC model, whereas Nanog and KLF4 showed modest variation. In TNBC cells, both <i>normal</i>- and <i>adjacent</i>-CM partially shifted MDA-MB-231 morphology toward a more epithelial-like state, decreasing caveolin-1 levels, while <i>adjacent</i>-CM increased MMP9 expression. Overall, these results reveal that adipose tissue-derived soluble factors exert significant and subtype-dependent effects on BC tumorigenicity.