Nanoscopic characterization of hepatocytes treated with normoxic and hypoxic tumor-derived exosomes

Tuoyu Ju; Fan Yang; Shuwei Wang; Jiajia Wang; Zhengxun Song; Hongmei Xu; Zuobin Wang; Yujuan Chen

doi:10.1016/j.micron.2022.103283

Nanoscopic characterization of hepatocytes treated with normoxic and hypoxic tumor-derived exosomes

Micron. 2022 Jul:158:103283. doi: 10.1016/j.micron.2022.103283. Epub 2022 Apr 9.

Authors

Tuoyu Ju¹, Fan Yang¹, Shuwei Wang², Jiajia Wang¹, Zhengxun Song¹, Hongmei Xu¹, Zuobin Wang³, Yujuan Chen⁴

Affiliations

¹ International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China; Jilin Provincial Key Laboratory for Multi-information Nano Detection & Handling of Single Cells, Changchun University of Science and Technology, Changchun 130022, China.
² Affiliated Hospital of Jilin Medical University, Jilin 132000, China.
³ International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China; Jilin Provincial Key Laboratory for Multi-information Nano Detection & Handling of Single Cells, Changchun University of Science and Technology, Changchun 130022, China; JR3CN & IRAC, University of Bedfordshire, Luton LU1 3JU, UK. Electronic address: wangz@cust.edu.cn.
⁴ International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China; Jilin Provincial Key Laboratory for Multi-information Nano Detection & Handling of Single Cells, Changchun University of Science and Technology, Changchun 130022, China. Electronic address: chenyujuan@cust.edu.cn.

PMID: 35483123
DOI: 10.1016/j.micron.2022.103283

Abstract

Hypoxia is a key factor in tumor microenvironments. Tumor-derived exosomes under hypoxia have their functions of communication between local and remote cells, and play an important role in tumor growth and metastasis. However, the effect of tumor-derived exosomes on cell structures and functions under hypoxia is unknown. In this work, the effects of exosomes derived from hepatocellular carcinoma cells (HCC-LM3) under normoxia (N-exos) and hypoxia (H-exos) environments on the biological and physical properties of target cells were stduied. The N-exos promoted the proliferation of hepatocytes (HL-7702) at 1.5 mg/mL, while the H-exos promoted the proliferation of hepatocytes at a lower concentration (1.0 mg/mL). After the cells cultured with the same concentrations of N-exos and H-exos for different time periods, the cell migration was enhanced. The stress fibers of the cells became loose and the cytoskeleton was rearranged, which were time dependent. The changes in morphological and mechanical parameters of the HL-7702 cells were detected by atomic force microscopy (AFM). The results showed that the cell edges became irregular and the filopodia were increased versus the exosomes treatment time. The heights and elastic moduli of cells were reduced. Compared with N-exos, H-exos had a more significant effect on the biological and physical properties of target cells. The results provide a method for studying how tumor-derived exosomes affect the interaction between tumor cells and their hypoxic microenvironment.

Keywords: Atomic force microscope (AFM); Hepatocytes; Mechanical parameters; Normoxia and hypoxia; Tumor-derived exosomes.

MeSH terms

Carcinoma, Hepatocellular*
Cell Proliferation
Exosomes*
Hepatocytes
Humans
Hypoxia
Liver Neoplasms*
Tumor Microenvironment