Distinctive features of cancer-associated fibroblasts expressing CD105, a novel biomarker for bone metastasis, in early-stage invasive ductal breast cancer

Abstract

Purpose: Cancer-associated fibroblasts (CAFs) are highly heterogeneous and critically influence breast cancer progression, yet functionally relevant stromal subpopulations remain poorly defined. This study investigates whether CD105 expression distinguishes fibroblast subsets with distinct mesenchymal stem–like properties and tumor-modulating functions within early-stage breast cancer. Methods: CD105(+)/CD34(-) and CD105(-)/CD34(-) fibroblast subpopulations were isolated from primary luminal breast tumors and analyzed for phenotypic, molecular, and functional characteristics, as well as for their effects on breast cancer cell behavior using in vitro assays, including conditioned media (CM) approaches. Results: Both fibroblast subpopulations displayed mesenchymal stem/stromal cell (MSC) characteristics; however, CD105(+)/CD34(-) fibroblasts displayed a more pronounced MSC–like phenotype, with enhanced proliferative capacity, altered oxidative status, and a distinct gene expression and secretory profile. CM from CD105(+)/CD34(-) fibroblasts more strongly promoted migration and proliferation and increased the expression of genes associated with stemness, osteogenic differentiation, bone mineralization, and osteoclastogenesis in luminal and triple-negative human breast cancer cell lines, compared with CM from CD105(-)/CD34(-) fibroblasts. Conclusion: These findings identify CD105 as a potential functional discriminator of breast CAF subpopulations and suggest that CD105(+) fibroblasts may preferentially support tumor progression and the acquisition of bone-related traits. This work provides new insight into CAF heterogeneity and its potential relevance for metastatic progression, and may also guide future therapeutic strategies and research directions.