Obesity-driven changes in breast tissue exhibit a pro-angiogenic extracellular matrix signature.

Autor:	Bamberg EE; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Maslanka M; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Vinod-Paul K; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Sams S; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Pollack E; Department of Radiology and Medical Imaging, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Conklin M; Department of Cell and Regenerative Biology, School of Medicine and Public Health, Carbone Cancer Center (Tumor Microenvironment Program), University of Wisconsin, Madison, WI, USA.; Laboratory for Optical and Computations Instrumentation, Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA., Kabos P; Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk:	angličtina
Zdroj:	Matrix biology plus [Matrix Biol Plus] 2024 Sep 22; Vol. 24, pp. 100162. Date of Electronic Publication: 2024 Sep 22 (Print Publication: 2024).
DOI:	10.1016/j.mbplus.2024.100162
Abstrakt:	Obesity has reached epidemic proportions in the United States, emerging as a risk factor for the onset of breast cancer and a harbinger of unfavorable outcomes [1], [2], [3]. Despite limited understanding of the precise mechanisms, both obesity and breast cancer are associated with extracellular matrix (ECM) rewiring [4], [5], [6]. Utilizing total breast tissue proteomics, we analyzed normal-weight (18.5 to < 25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ), and obese (≥30 kg/m 2 ) individuals to identify potential ECM modifying proteins for cancer development and acceleration. Obese individuals exhibited substantial ECM alterations, marked by increased basement membrane deposition, angiogenic signatures, and ECM-modifying proteins. Notably, the collagen IV crosslinking enzyme peroxidasin (PXDN) emerged as a potential mediator of the ECM changes in individuals with an elevated body mass index (BMI), strongly correlating with angiogenic and basement membrane signatures. Furthermore, glycan-binding proteins galectin-1 (LGALS1) and galectin-3 (LGALS3), which play crucial roles in matrix interactions and angiogenesis, also strongly correlate with ECM modifications. In breast cancer, elevated PXDN, LGALS1, and LGALS3 correlate with reduced relapse-free and distant-metastatic-free survival. These proteins were significantly associated with mesenchymal stromal cell markers, indicating adipocytes and fibroblasts may be the primary contributors of the obesity-related ECM changes. Our findings unveil a pro-angiogenic ECM signature in obese breast tissue, offering potential targets to inhibit breast cancer development and progression. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Kabos reports financial support was provided by National Cancer Institute. Ellen Bamberg reports financial support was provided by National Cancer Institute. Kirk Hansen reports financial support was provided by University of Colorado Cancer Center. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier B.V.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu