Investigation of Cancer Cell Migration and Proliferation on Synthetic Extracellular Matrix Peptide Hydrogels

Abstract

Chemical and mechanical properties of a tumor microenvironment are essential players in cancer progression, and it is important to precisely control the extracellular conditions while designing cancer in vitro models. The study investigates synthetic hydrogel matrices from multi-arm polyethylene glycol (PEG) functionalized with collagen-like peptide (CLP) CG(PKG) 4 (POG) 4 (DOG) 4 alone and conjugated with either cell adhesion peptide RGD (mimicking fibronectin) or IKVAV (mimicking laminin). Human glioblastoma HROG36, rat C6 glioma cells, and A375 human melanoma cells were grown on the hydrogels and monitored for migration, proliferation, projected cell area, cell shape index, size and number, distribution of focal contacts in individual cells, and focal adhesion number. PEG-CLP-RGD induced migration of both glioma cell lines and also stimulated proliferation (assessed as metabolic activity) of HROG36 cells. Migration of C6 cells were also stimulated by PEG-CLP-IKVAV. These responses strongly correlated with the changes in adhesion and morphology parameters of individual cells-projected cell area, cell shape index, and focal contact number. Melanoma A375 cell proliferation was increased by PEG-CLP-RGD, and this was accompanied by a decrease in cell shape index. However, neither RGD nor IKVAV conjugated to PEG-CLP stimulated migratory capacity of A375 cells. Taken together, the study presents synthetic scaffolds with extracellular matrix (ECM)-mimicking peptides that allow for the exploration of the effect of ECM signaling to cancer cells.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability

“…Cell migration is altered by the biphasic hydrogel phenomenon associated with ligand density and cell adhesion, causing a traction force to be exerted on the substrate to move the cell [17,32]. It has been reported that focal adhesion affects cell migration due to mechanical stimuli obtained from the environment [33][34][35]. In this case, integrins as receptors will target the ECM by transmitting both outside-in signals and inside-out signals [33].…”

“…It has been reported that focal adhesion affects cell migration due to mechanical stimuli obtained from the environment [33][34][35]. In this case, integrins as receptors will target the ECM by transmitting both outside-in signals and inside-out signals [33]. Other studies have shown that the use of RGD peptides has the potential to inhibit cell migration [36].…”

Supramolecular Peptide Nanofiber Hydrogels for Bone Tissue Engineering: From Multihierarchical Fabrications to Comprehensive Applications

“…Most importantly, bioactive motifs, such as RGD and isoleucine‐lysine‐valine‐alanine‐valine (IKVAV), could be conjugated to CMPs. [ 111 ]…”

Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

“…Actually, peptide-based hydrogels have already shown their potential as a matrix for cell culture experiments creating adequate 3D microenvironments [ 137 , 138 , 139 , 140 ]. It has been demonstrated that they promote cell differentiation, stem cell proliferation, support the attachment of different kinds of cells, can be used for angiogenesis assays, and tumor cell migration and invasion tests [ 141 , 142 , 143 , 144 , 145 , 146 ]. Some hydrogel formulations are already in the market (e.g., Puramatrix, Hydromatrix, TrueGel3D).…”