Coevolution of Prostate Cancer and Bone Stroma in Three-Dimensional Coculture: Implications for Cancer Growth and Metastasis

Abstract

Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes with reactive oxygen species serving as mediators. The evolved stromal cells are highly inductive of human PCa growth in mice, and expressed increased levels of extracellular matrix (versican and tenascin) and chemokine (BDFN, CCL5, CXCL5, and CXCL16) genes. These genes were validated in clinical tissue and/or serum specimens and could be the predictors for invasive and bone metastatic PCa. These results, combined with our previous observations, support the concept of permanent genetic and behavioral changes of PCa epithelial cells after being either cocultured with prostate or bone stromal cells as three-dimensional prostate organoids or grown as tumor xenografts in mice. These observations collectively suggest coevolution of cancer and stromal cells occurred under three-dimensional growth condition, which ultimately accelerates cancer growth and metastasis.

Establishment and characterization of a pair of non-malignant and malignant tumor derived cell lines from an African American prostate cancer patient

“…Formation of non-adherent three dimensional organoids could possibly serve as a criterion for in vitro tumor forming potential (13,14). In order to determine whether cells demonstrated this characteristic, 2x10 7 of both RC-77N/E and RC-77T/E cells were introduced to the RWV system.…”

Radixin regulates cell migration and cell-cell adhesion through Rac1

“…3C). Similarly, bcatenin, which binds directly to cadherin cytoplasmic tails (Shapiro and Weis, 2009;Sung et al, 2008), was localised to sites of cell-cell contact in radixin-depleted cells, whereas in control cells it was homogenously distributed throughout the cytoplasm (Fig. 3C).…”

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

“…The hTERT immortalized fibroblast (Pf179T), epithelial (Ep156T), and smooth muscle (Pm151T) cell lines were provided by V. Rotter (Weizmann Institute of Science, Israel) and cultured in conditions as recommended (19). The human primary (nonimmortalized) prostate fibroblast cells isolated from normal (Pt-N) or cancerous (Pt-C) tissues of prostate cancer patients were kind gifts of L. Chung (Emory University) and were cultured as described previously (39). The primary prostate epithelial cell line (PrEC) was purchased from Lonza (Walkersville, MD) and cultured in conditions as recommended by the supplier.…”

“…We used a series of telomeraseimmortalized primary cell lines of the epithelial (Ep156T), smooth muscle (Pm151T), and fibroblast (Pf179T) origins that were previously derived from healthy human prostate glands (19). In addition, we also used nonimmortalized fibroblast cell lines, Pt-N and Pt-C, which were derived from benign and malignant prostate tissues, respectively (39), and the established primary prostatic epithelial PrEC cells (Lonza). Even though most of the telomerase-immortalized cell lines used in the present study, except for the Pf179T, have been characterized (19), we validated the cell-type origins of these and most other primary cell lines used in the present study by determining the expression of the specific protein markers by Western blot analysis with the appropriate antibodies.…”