Abstract C9: An in vitro model of osteoblastic bone metastasis in prostate cancer

Abstract

Abstract Prostate cancer progression is characterized by a striking affinity to spread to bone, where it forms metastases predominately of an osteoblastic phenotype, resulting in a significant source of morbidity. Currently, animal models for studying the development of these osteoblastic metastases are limited due to a lack of spontaneous osteoblastic metastasis development. In order to recapitulate osteoblastic metastasis development, an in vitro, three dimensional culture system was created utilizing silk fibroin scaffolds. LNCaP cells were seeded to silk scaffolds with human bone marrow derived mesenchymal stem cells (hMSCs) and cultured for 6 weeks. Examination after co-culture revealed through histological analysis that hMSCs underwent osteogenic differentiation in response to LNCaP paracrine signals. Paracrine interactions between hMSCs and LNCaPs were studied and IL-6, known to promote androgen independent growth, was found to be transiently expressed by hMSCs over the first two weeks of co-culture. In addition to secreted soluble signaling factors, the effect of extracellular matrix signals on the LNCaP cells was examined. LNCaP cells grown in a decellularized matrix, derived from hMSCs having undergone osteogenic differentiation, showed a 12 fold survival advantage in androgen depleted conditions over controls. This data indicates the ability of the co-culture system to stimulate differentiation of hMSCs towards an osteogenic linage and release soluble and extracellular matrix cues which stimulate androgen independent disease progression. The in vitro co-culture system presents a scalable and high throughput method for studying the molecular mechanisms underlying the osteoblastic component of prostate cancer bone metastasis. Citation Information: Cancer Res 2009;69(23 Suppl):C9.