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

## TL;DR

This study identifies CD105 as a marker for a specific type of cancer-associated fibroblast that promotes breast cancer progression and bone metastasis traits.

## Contribution

CD105 is proposed as a novel biomarker for bone metastasis in early-stage breast cancer.

## Key findings

- CD105(+)/CD34(-) fibroblasts show enhanced mesenchymal stem-like features and pro-tumoral activity.
- Conditioned media from CD105(+) fibroblasts increase cancer cell migration, proliferation, and bone-related gene expression.
- CD105(+) fibroblasts may support tumor progression and metastatic traits, offering new therapeutic insights.

## Abstract

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.

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.

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.

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.

Summary of the key findings of the study. This figure highlights the main results and conclusions drawn from the research.Infographic illustrating the characterization of cancer-associated fibroblasts (CAFs) in breast cancer, outlining phenotypic markers, functional characterization such as growth and gene expression, pro-tumoral activities including migration and proliferation stimulation, and highlighting stemness, osteogenic differentiation, and potential biomarker and drug target roles.

Summary of the key findings of the study. This figure highlights the main results and conclusions drawn from the research.