title: Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape.
abstract: Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer models. Tumors engineered in biomaterial scaffolds have shown evidence of being more physiologically relevant than some traditional preclinical model systems, and synthetic biomaterials provide the added benefit of defined and consistent microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre-cultured with tumorigenic M12 cells prior to implantation generated tumors in athymic nude mice, demonstrating the ability of the scaffolds to be used as a synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4-2 cells, which require Matrigel or stromal cell support for tumor formation, were poorly tumorigenic up to 12 weeks after implantation even when Matrigel was infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily rendered non-tumorigenic through the expression of the tumor suppressor insulin-like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed significant macrophage infiltration within the scaffolds driven by the foreign body response to the materials. These findings show the potential for this biomaterials-based model system to be used in the study of prostate cancer tumorigenesis and dormancy escape.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Long
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Sprenger
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Plymate
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: ratner@uweb.engr.washington.edu.
authors.forename: Buddy D
authors.initials: BD
authors.lastname: Ratner
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D006801:Humans; D021621:Imaging, Three-Dimensional; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007797:Laminin / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D009368:Neoplasm Transplantation; D011102:Polyhydroxyethyl Methacrylate / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000628:therapy*; D011509:Proteoglycans / Q000737:chemistry; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D018969:Insulin-Like Growth Factor Binding Proteins; D007797:Laminin; D011509:Proteoglycans; C102529:insulin-like growth factor binding protein-related protein 1; C059485:matrigel; D011102:Polyhydroxyethyl Methacrylate; D003094:Collagen
keywords: Dormancy; PolyHEMA; Prostate cancer; Scaffold; Tumor microenvironment; Xenograft