Here, we demonstrate the flexibility of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels for modeling tumor progression. The PEG hydrogels were formed using thiol-ene chemistry to incorporate a matrix metalloproteinase-degradable peptide crosslinker (KKCGGPQG↓IWGQGCKK) permissive to proteolytic remodeling and the adhesive CRGDS peptide ligand. Tumor cell function was investigated by culturing WM239A melanoma cells on PEG hydrogel surfaces or encapsulating cells within the hydrogels and either as monocultures or indirect (non-contact) cocultures with primary human dermal fibroblasts (hDFs). WM239A cluster size and proliferation rate depended on the shear elastic modulus for cells cultured on PEG hydrogels, while growth was inhibited by coculture with hDFs regardless of hydrogel stiffness. Cluster size was also suppressed by hDFs for WM239A cells encapsulated in PEG hydrogels, which is consistent with cells seeded on top of hydrogels. Notably, encapsulated WM239A clusters and single cells adopted invasive phenotypes in the hDF coculture model, which included single cell and collective migration modes that resembled invasion from human melanoma patient-derived xenograft tumors encapsulated in equivalent PEG hydrogels. Our combined results demonstrate that peptide-functionalized PEG hydrogels provide a useful platform for investigating aspects of tumor progression in 2D and 3D microenvironments, including single cell migration, cluster growth and invasion.
A synthetic modular approach for modeling the role of the 3D microenvironment in tumor progression
Samir P. Singh,Michael P. Schwartz,E. Tokuda,Yuhuan Luo,Robert E Rogers,M. Fujita,Natalie G. Ahn,K. Anseth
Published 2015 in Scientific Reports
ABSTRACT
PUBLICATION RECORD
- Publication year
2015
- Venue
Scientific Reports
- Publication date
2015-12-07
- Fields of study
Medicine, Chemistry
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- crgds peptide ligand
An adhesive RGD-containing peptide incorporated into the hydrogel to provide cell-binding sites.
Aliases: CRGDS
- indirect coculture
A non-contact coculture setup in which WM239A cells and fibroblasts share medium but are not physically mixed.
Aliases: non-contact coculture
- matrix metalloproteinase-degradable peptide crosslinker
A peptide crosslinker containing an MMP-cleavable sequence that makes the hydrogel network permissive to proteolytic remodeling.
Aliases: MMP-degradable peptide crosslinker, KKCGGPQG↓IWGQGCKK
- patient-derived xenograft tumors
Melanoma tumors propagated in xenograft models and encapsulated in comparable PEG hydrogels for invasion comparison.
Aliases: PDX tumors
- peptide-functionalized peg hydrogels
Synthetic poly(ethylene glycol) hydrogel matrices functionalized with peptide cues and formed by thiol-ene crosslinking in this work.
Aliases: PEG hydrogels, peptide-functionalized poly(ethylene glycol) hydrogels
- primary human dermal fibroblasts
Primary human fibroblasts from dermal tissue used as the non-contact coculture partner.
Aliases: hDFs
- shear elastic modulus
The mechanical stiffness measure used to characterize the PEG hydrogel surfaces and compare different substrate rigidities.
Aliases: stiffness
- thiol-ene chemistry
A light-driven click chemistry used to form the PEG hydrogel network from reactive components.
- wm239a melanoma cells
A human melanoma cell line used as the tumor cell model in the hydrogel experiments.
Aliases: WM239A cells
REFERENCES
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