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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Cancer Endocrinology

This article is part of the Research TopicUnderstanding the Breast Tumor Microenvironment: Advances in Emerging Biomarkers and Molecular Targets for Precision OncologyView all articles

Distinctive Features of Cancer-Associated Fibroblasts Expressing CD105, a Novel Biomarker for Bone Metastasis, in Early-Stage Invasive Ductal Breast Cancer

Provisionally accepted
Maria Belen GiorelloMaria Belen Giorello1*Francisco Raúl BorzoneFrancisco Raúl Borzone1,2Cecilia SanmartinCecilia Sanmartin1Leandro MartinezLeandro Martinez3Mrinmoy SarkarMrinmoy Sarkar4Tapasree Roy SarkarTapasree Roy Sarkar4Vivian LabovskyVivian Labovsky1Alejandra WernickeAlejandra Wernicke5Norma Alejandra ChasseingNorma Alejandra Chasseing1*
  • 1Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)., Buenos Aires, Argentina
  • 2Laboratorio de Medicina Regenerativa Cardiovascular, Instituto de Medicina Traslacional, Trasplante y Bioingeniería (IMETTyB-Universidad Favaloro-CONICET), Ciudad Autonoma de Buenos Aires, Argentina
  • 3Weill Cornell Medicine Division of Hematology and Medical Oncology, New York, United States
  • 4Department of Biology, Faculty, Genetics and Genomics, Center for Biological Clock Research (CBCR), Texas A&M University, College Station, United States
  • 5Departamento de Anatomía Patológica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

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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.

Keywords: breast cancer, cancer-associated fibroblasts, CD105, metastasis, osteoblast-like cancer cells, stemness genes induction

Received: 12 Dec 2025; Accepted: 03 Feb 2026.

Copyright: © 2026 Giorello, Borzone, Sanmartin, Martinez, Sarkar, Roy Sarkar, Labovsky, Wernicke and Chasseing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Maria Belen Giorello
Norma Alejandra Chasseing

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