Tuning Hydrogel Adhesivity and Degradability to Model the Influence of Premetastatic Niche Matrix Properties on Breast Cancer Dormancy and Reactivation

• Published in: Advanced biology 2022-05, Vol.6 (5), p.e2200012-n/a
• Main Authors: Farino Reyes, Cindy J., Slater, John H.
• Format: Article
• Language: English
• Subjects: Adhesives; Breast Neoplasms - pathology; cancer; cancer metastasis; disseminated tumor cells; extracellular matrix; Female; Humans; Hydrogels - pharmacology; Polyethylene Glycols; tissue engineering
• ISSN: 2701-0198; 2701-0198
• DOI: 10.1002/adbi.202200012

Dormant, disseminated tumor cells (DTCs) can persist for decades in secondary tissues before being reactivated to form tumors. The properties of the premetastatic niche can influence the DTC phenotype. To better understand how matrix properties of premetastatic niches influence DTC behavior, three hydrogel formulations are implemented to model a permissive niche and two nonpermissive niches. Poly(ethylene glycol) (PEG)‐based hydrogels with varying adhesivity ([RGDS]) and degradability ([N‐vinyl pyrrolidinone]) are implemented to mimic a permissive niche with high adhesivity and degradability and two nonpermissive niches, one with moderate adhesivity and degradability and one with no adhesivity and high degradability. The influence of matrix properties on estrogen receptor positive (ER+) breast cancer cells (MCF7s) is determined via a multimetric analysis. MCF7s cultured in the permissive niche adopted a growth state, while those in the nonpermissive niche with reduced adhesivity and degradability underwent tumor mass dormancy. Complete removal of adhesivity while maintaining high degradability induced single cell dormancy. The ability to mimic reactivation of dormant cells through a dynamic increase in [RGDS] is also demonstrated. This platform provides the capability of inducing growth, dormancy, and reactivation of ER+ breast cancer and can be useful in understanding how premetastatic niche properties influence cancer cell fate. An in vitro platform that induces dormancy and reactivation is a useful tool in drug development to eliminate dormant cancer and prevent metastatic relapse. In this study, three hydrogel formulations mimic a permissive and two nonpermissive niches by tuning ligand (RGDS) density and degradability to induce growth, distinct forms of dormancy, and reactivation in ER+, MCF7s are implemented.