title: Tissue engineering a surrogate niche for metastatic cancer cells.
abstract: In breast and prostate cancer patients, the bone marrow is a preferred site of metastasis. We hypothesized that we could use tissue-engineering strategies to lure metastasizing cancer cells to tissue-engineered bone marrow. First, we generated highly porous 3D silk scaffolds that were biocompatible and amenable to bone morphogenetic protein 2 functionalization. Control and functionalized silk scaffolds were subcutaneously implanted in mice and bone marrow development was followed. Only functionalized scaffolds developed cancellous bone and red bone marrow, which appeared as early as two weeks post-implantation and further developed over the 16-week study period. This tissue-engineered bone marrow microenvironment could be readily manipulated in situ to understand the biology of bone metastasis. To test the ability of functionalized scaffolds to serve as a surrogate niche for metastasis, human breast cancer cells were injected into the mammary fat pads of mice. The treatment of animals with scaffolds had no significant effect on primary tumor growth. However, extensive metastasis was observed in functionalized scaffolds, and the highest levels for scaffolds that were in situ manipulated with receptor activator of nuclear factor kappa-B ligand (RANKL). We also applied this tissue-engineered bone marrow model in a prostate cancer and experimental metastasis setting. In summary, we were able to use tissue-engineered bone marrow to serve as a target or "trap" for metastasizing cancer cells.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
authors.forename: F Philipp
authors.initials: FP
authors.lastname: Seib
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Berry
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shiozawa
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
authors.affiliation: Tufts University, Department of Biomedical Engineering, 4 Colby Street Medford, MA 02155, USA. Electronic address: David.Kaplan@tufts.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology; D023822:Tissue Engineering / Q000379:methods*
keywords: Bone; Breast cancer; Cancer; Metastasis; Silk