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Updated: Jul 15, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
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Matrix Stiffness Regulated Endoplasmic Reticulum Stress-mediated Apoptosis of Osteosarcoma Cell through Ras Signal

Huan Deng1, Xuedong Shu1, Yao Wang1

  • 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, PR China.

Cell Biochemistry and Biophysics
|October 3, 2023
PubMed

Insights

Matrix stiffness influences tumor cell spreading and apoptosis. This study reveals how mechanical cues regulate cancer cell fate via cytoskeletal organization and specific signaling pathways, impacting endoplasmic reticulum stress.

Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Cancer Research

Background:

  • Matrix stiffness is known to affect tumor cell behavior, including spreading and apoptosis.
  • The precise mechanisms and pathways governing matrix stiffness-induced cancer cell apoptosis remain incompletely understood.

Purpose of the Study:

  • To investigate the detailed mechanisms by which matrix stiffness modulates tumor cell spreading and apoptosis.
  • To elucidate the role of cytoskeletal organization and specific signaling pathways in this process.

Main Methods:

  • Fabrication of tunable elastic hydrogel matrices (1, 10, 30, 250 kPa) with modified polyacrylamide surfaces.
  • Culturing MG-63 cells on matrices of varying stiffness to assess cell adhesion, spreading, and apoptosis.
  • Analysis of signaling pathways including Ras, Rap1, and PI3K-Akt, and endoplasmic reticulum stress markers.

Main Results:

  • Cell spreading increased, while apoptosis decreased with increasing matrix stiffness, but with complex time-dependent behaviors.
  • Similar apoptosis rates were observed for 30 kPa and 250 kPa matrices, suggesting non-linear responses.
  • Matrix stiffness regulated cell adhesion and cytoskeletal organization, impacting Ras, Rap1, and PI3K-Akt pathways, ultimately leading to apoptosis via endoplasmic reticulum stress.

Conclusions:

  • Matrix stiffness plays a critical role in regulating cancer cell fate by influencing cell adhesion and cytoskeletal organization.
  • The findings provide insights into the mechanical regulation of tumor cell apoptosis, highlighting the involvement of specific signaling pathways and endoplasmic reticulum stress.
  • This research has implications for understanding the tumor microenvironment and designing novel anticancer materials.
Keywords:
ApoptosisER-StressOsteosarcomaSpreadingStiffness

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