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转录组应答酸中毒揭示其对乳腺癌细胞骨转移的贡献。

Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells.

机构信息

Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.

Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.

出版信息

Cells. 2022 Feb 4;11(3):544. doi: 10.3390/cells11030544.

DOI:10.3390/cells11030544
PMID:35159353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8834614/
Abstract

Bone is the most common site of metastasis in breast cancer. Metastasis is promoted by acidosis, which is associated with osteoporosis. To investigate how acidosis could promote bone metastasis, we compared differentially expressed genes (DEGs) in MDA-MB-231 cancer cells in acidosis, bone metastasis, and bone metastatic tumors. The DEGs were identified using Biojupies and GEO2R. The expression profiles were assessed with Morpheus. The overlapping DEGs between acidosis and bone metastasis were compared to the bulk of the DEGs in terms of the most important genes and enriched terms using CytoHubba and STRING. The expression of the genes in this overlap filtered by secreted proteins was assessed in the osteoporosis secretome. The analysis revealed that acidosis-associated transcriptomic changes were more similar to bone metastasis than bone metastatic tumors. Extracellular matrix (ECM) organization would be the main biological process shared between acidosis and bone metastasis. The secretome genes upregulated in acidosis, bone metastasis, and osteoporosis-associated mesenchymal stem cells are enriched for ECM organization and angiogenesis. Therefore, acidosis may be more important in the metastatic niche than in the primary tumor. Acidosis may contribute to bone metastasis by promoting ECM organization. Untreated osteoporosis could favor bone metastasis through the increased secretion of ECM organization proteins.

摘要

骨骼是乳腺癌最常见的转移部位。转移是由酸中毒促进的，而酸中毒与骨质疏松症有关。为了研究酸中毒如何促进骨转移，我们比较了 MDA-MB-231 癌细胞在酸中毒、骨转移和骨转移性肿瘤中的差异表达基因（DEGs）。使用 Biojupies 和 GEO2R 识别 DEGs。使用 Morpheus 评估表达谱。使用 CytoHubba 和 STRING 比较酸中毒和骨转移之间的重叠 DEGs 与大量 DEGs 在最重要的基因和富集术语方面的差异。通过骨质疏松症分泌组评估此重叠中经分泌蛋白过滤的基因的表达。分析表明，酸中毒相关的转录组变化与骨转移比骨转移性肿瘤更相似。细胞外基质（ECM）组织将是酸中毒和骨转移之间共享的主要生物学过程。在酸中毒、骨转移和骨质疏松症相关间充质干细胞中上调的分泌组基因富集 ECM 组织和血管生成。因此，酸中毒在转移灶中可能比在原发性肿瘤中更为重要。酸中毒可能通过促进 ECM 组织来促进骨转移。未经治疗的骨质疏松症可能通过增加 ECM 组织蛋白的分泌而有利于骨转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/31099a5f6405/cells-11-00544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/484841837474/cells-11-00544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/bb83a5ce0f20/cells-11-00544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/afd41e10401e/cells-11-00544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/62e4768d97ec/cells-11-00544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/d31f449970e2/cells-11-00544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/38dff2ff51e0/cells-11-00544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/31099a5f6405/cells-11-00544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/484841837474/cells-11-00544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/bb83a5ce0f20/cells-11-00544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/afd41e10401e/cells-11-00544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/62e4768d97ec/cells-11-00544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/d31f449970e2/cells-11-00544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/38dff2ff51e0/cells-11-00544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/8834614/31099a5f6405/cells-11-00544-g007.jpg

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