Differential bone morphology and hypoxia activity in skeletal metastases of ER + and ER - breast cancer.

Autor: Das A; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Barry MM; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Ernst CA; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Dahiya R; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Kim M; Comparative Oncology Shared Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Rosario SR; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Lo HC; Lester and Sue Smith Breast Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Yu C; Lester and Sue Smith Breast Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Dai T; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Gugala Z; Department of Orthopedic Surgery & Rehabilitation, University of Texas Medical Branch, Galveston, TX, USA., Zhang J; Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.; Department of Cell and Cancer Biology, University of Toledo, Toledo, OH, USA., Dasgupta S; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Wang H; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. Hai.Wang@Roswellpark.org.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Nov 21; Vol. 7 (1), pp. 1545. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s42003-024-07247-6
Abstrakt: Bone metastases occur in the majority of advanced breast cancer patients, and the most common complications are osteolytic bone metastases. However, due to the limitations of models and methodologies for bone metastasis studies, the intricacies of bone metastasis have not been fully acknowledged and revealed in prior work. Our earlier study indicated that certain breast cancer cells undergo a pre-osteolytic stage before the establishment of overt metastatic lesions. Here, we further identify a differential bone morphology between ER (estrogen receptor) + and ER - breast cancer. Specifically, we observe a more pronounced osteolytic phenotype in the bone metastatic lesions of ER - cells investigated, linked to elevated hypoxia signaling that stimulates the secretion of osteolytic inducers from cancer cells. In the in vivo mouse model, the application of the hypoxia-inducible factor (HIF) inhibitor 2-methoxyestradiol demonstrates a promising efficacy in suppressing tumor growth and osteoclast differentiation in the bone lesions established by bone-tropic subpopulation of ER - MDA-MB-231 cell. Overall, our findings explore the complexity of phenotype and morphology in bone metastatic lesions of ER + and ER - breast cancer, which offers a compelling rationale for leveraging HIF inhibitors to the treatment targeting skeletal complications of breast cancer bone metastases, especially for ER - tumors.
Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: All co-authors of this publication have met the criteria for authorship required by Nature Portfolio journals as reported in the contributions section and as agreed among collaborators beforehand. This research did not include medical research involving human participants or local partners. This research was not severely restricted or prohibited in the setting of the researchers and does not result in stigmatization, incrimination, discrimination, or personal risk to participants. Informed consent: All participants provided written informed consent at enrollment.
(© 2024. The Author(s).)
Databáze: MEDLINE
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