2. Academic Validation
  3. Transcriptomics and metabolomics reveal changes in the regulatory mechanisms of osteosarcoma under different culture methods in vitro

Transcriptomics and metabolomics reveal changes in the regulatory mechanisms of osteosarcoma under different culture methods in vitro

  • BMC Med Genomics. 2022 Dec 19;15(1):265. doi: 10.1186/s12920-022-01419-1.
Sen Yang # 1 2 3,  Zhi Tian # 1 2,  Yi Feng # 1 2,  Kun Zhang 1 2,  Yongchun Pan 4,  Yuan Li 1 2,  Zhichao Wang 5,  Wenhao Wei 1 2,  Xiaochen Qiao 1 2 6,  Ruhao Zhou 1 2,  Lei Yan 1 2,  Qian Li 1 2,  Hua Guo 1 2,  Jie Yuan 1 2,  Pengcui Li 1 2,  Zhi Lv 7 8
Affiliations

Affiliations

  • 1 Second Clinical Medical College, Shanxi Medical University, 382 Wuyi Road, Shanxi, 030001, Taiyuan, People's Republic of China.
  • 2 Department of Orthopedics, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Shanxi, 030001, Taiyuan, People's Republic of China.
  • 3 Department of Orthopedics, The Second People's Hospital of Changzhi City, 83 Peace West Street, Shanxi, 046000, Changzhi, People's Republic of China.
  • 4 Department of Orthopedics, The Third people's Hospital of Datong City, Shanxi, 037006, Datong, People's Republic of China.
  • 5 Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, 030032, Taiyuan, People's Republic of China.
  • 6 Department of Orthopedics, JinZhong Hospital Affiliated to Shanxi Medical University, 689 Huitong South Road, Shanxi, 030600, Jinzhong, People's Republic of China.
  • 7 Second Clinical Medical College, Shanxi Medical University, 382 Wuyi Road, Shanxi, 030001, Taiyuan, People's Republic of China. zhilv2013@163.com.
  • 8 Department of Orthopedics, Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Shanxi, 030001, Taiyuan, People's Republic of China. zhilv2013@163.com.
  • # Contributed equally.
PMID: 36536381 DOI: 10.1186/s12920-022-01419-1
Abstract

Background: Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo.

Methods: We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods.

Results: At the transcriptional level, 166 differentially expressed genes were found, including the Smad Family, ID family, BMP family and Other related genes, and they were enriched in the TGF-β signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, Ferroptosis, cGMP-PKG signaling pathway and Other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, Ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were Ferroptosis and pyrimidine metabolism.

Conclusion: Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the Ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.

Keywords

Metabolomics; Osteosarcoma; Transcriptomics; Tumor microenvironment.

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