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  3. Physical Cues in the Microenvironment Regulate Stemness-Dependent Homing of Breast Cancer Cells

Physical Cues in the Microenvironment Regulate Stemness-Dependent Homing of Breast Cancer Cells

  • Cancers (Basel). 2020 Aug 5;12(8):2176. doi: 10.3390/cancers12082176.
Hsueh-Yao Chu 1,  Yin-Ju Chen 2 3 4,  Chun-Jieh Hsu 1,  Yang-Wei Liu 1,  Jeng-Fong Chiou 2 5 6,  Long-Sheng Lu 2 3 4 7,  Fan-Gang Tseng 1 8 9
Affiliations

Affiliations

  • 1 Department of Engineering and System Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • 2 Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 11031, Taiwan.
  • 3 Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
  • 4 International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
  • 5 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 6 Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan.
  • 7 International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 8 Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing-Hua University, Hsinchu 30013, Taiwan.
  • 9 Research Center for Applied Sciences, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nankang, Taipei 11529, Taiwan.
PMID: 32764400 DOI: 10.3390/cancers12082176
Abstract

Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic cancers. However, the physical attributes of the premetastatic microenvironment are not yet fully characterized. In this research, we develop a transwell-based alginate hydrogel (TAH) model to study how permeability, stiffness, and roughness of a hanging alginate hydrogel regulate breast Cancer cell homing. In this model, a layer of physically characterized alginate hydrogel is formed at the bottom of a transwell insert, which is placed into a matching culture well with an adherent monolayer of breast Cancer cells. We found that breast Cancer cells dissociate from the monolayer and home to the TAH for continual growth. The process is facilitated by the presence of rich serum in the upper chamber, the increased stiffness of the gel, as well as its surface roughness. This model is able to support the homing ability of MCF-7 and MDA-MB-231 cells drifting across the vertical distance in the culture medium. Cells homing to the TAH display stemness phenotype morphologically and biochemically. Taken together, these findings suggest that permeability, stiffness, and roughness are important physical factors to regulate breast Cancer homing to a premetastatic microenvironment.

Keywords

cell homing; extracellular matrix; hydrogel; nanotopography; stiffness; tumor microenvironment.

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