期刊
BIOMATERIALS
卷 34, 期 37, 页码 9486-9495出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.08.077
关键词
Breast cancer; Invasion; Dissemination; Poly(ethylene) glycol hydrogels; Mechanical properties; Cell adhesion
资金
- Maryland Stem Cell Research Foundation
- National Science Foundation [CMMI 0948053]
- Safeway Foundation Award for Breast Cancer Research
- National Institutes of Health [1F31AG034016, NIDCR R01DE016887, NCI U01 CA155758, NCI U54 CA151838]
- American Cancer Society [RSG-12-141-01-CSM]
Metastasis begins with the escape, or dissemination, of cancer cells from the primary tumor. We recently demonstrated that tumors preferentially disseminate into collagen I and not into basement membrane protein gels (Matrigel). In this study, we used synthetic polymer systems to define material properties that could induce dissemination into Matrigel. We first specifically varied rigidity by varying the crosslinking density of poly(ethylene glycol) (PEG) networks within Matrigel scaffolds. Increased microenvironmental rigidity limited epithelial growth but did not promote dissemination. We next incorporated adhesive signals into the PEG network using peptide-conjugated cyclodextrin (alpha-CDYRGDS) rings. The a-CDYRGDS rings threaded along the PEG polymers, enabling independent control of matrix mechanics, adhesive peptide composition, and adhesive density. Adhesive PEG networks induced dissemination of normal and malignant mammary epithelial cells at intermediate values of adhesion and rigidity. Our data reveal that microenvironmental signals can induce dissemination of normal and malignant epithelial cells without requiring the fibrillar structure of collagen I or containing collagen I-specific adhesion sequences. Finally, the nanobiomaterials and assays developed in this study are generally useful both in 3D culture of primary mammalian tissues and in the systematic evaluation of the specific role of mechanical and adhesive inputs on 3D tumor growth, invasion, and dissemination. (C) 2013 Elsevier Ltd. All rights reserved.
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