Extracellular Mechanical Stimuli Alters the Metastatic Progression of Prostate Cancer Cells within 3D Tissue Matrix

Abstract

This study aimed to understand extracellular mechanical stimuli’s effect on prostate cancer cells’ metastatic progression within a three-dimensional (3D) bone-like microenvironment. In this study, a mechanical loading platform, EQUicycler, has been employed to create physiologically relevant static and cyclic mechanical stimuli to a prostate cancer cell (PC-3)-embedded 3D tissue matrix. Three mechanical stimuli conditions were applied: control (no loading), cyclic (1% strain at 1 Hz), and static mechanical stimuli (1% strain). The changes in prostate cancer cells’ cytoskeletal reorganization, polarity (elongation index), proliferation, expression level of N-Cadherin (metastasis-associated gene), and migratory potential within the 3D collagen structures were assessed upon mechanical stimuli. The results have shown that static mechanical stimuli increased the metastasis progression factors, including cell elongation (p < 0.001), cellular F-actin accumulation (p < 0.001), actin polymerization (p < 0.001), N-Cadherin gene expression, and invasion capacity of PC-3 cells within a bone-like microenvironment compared to its cyclic and control loading counterparts. This study established a novel system for studying metastatic cancer cells within bone and enables the creation of biomimetic in vitro models for cancer research and mechanobiology.

Nanostructured Biomaterials in Tumor Tissue Engineering: Regenerative Medicine and Immunotherapies

“…Metastatic tumor cells are affected by mechanical extracellular factors within the bone microenvironment, including matrix stiffness through stromal activation, interstitial fluid pressure, constant pressure owing to tumor growth, cell-cell and cell-ECM interactions. Ditto et al [95], studied the effect of extracellular bone-like mechanical stimuli on the metastatic potential of bone metastasis prostatic adenocarcinoma PC-3 cells that were embedded in a 3D collagen type I scaffold. Mechanical strain was applied on the 3D scaffold through an EQUicycler system, in order to study the effect of the mechanical stimuli on cytoskeletal organization, proliferation and invasion of PC-3 cells.…”