Sung S-Y, Hsieh C-L, Law A, Zhau HE, Pathak S, Multani AS, Lim S, Coleman IM, Wu L-C, Figg WD, Dahut WL, Nelson P, Lee JK, Amin MB, Lyles R, Johnstone PAJ, Marshall FF, Chung LWKCoevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis. Cancer Res 68: 9996-10003

Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Cancer Research (Impact Factor: 9.33). 01/2009; 68(23):9996-10003. DOI: 10.1158/0008-5472.CAN-08-2492
Source: PubMed


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.

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Available from: Asha S Multani
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    • "Tumoroids [172] Mixed spheroids [173] Nodules [174] Heterospheroids [175] Organoids [28] Tumorospheres Spheroids [40] Colospheres [43] [44] Spheres [30] [34] [36] [38] [39] Tumorspheres [30] Oncospheres [34] Xenospheres (from patient tumor-derived xenografts) [176] Neurospheres (normal and malignant brain) [35] [36] Mammospheres (normal and malignant breast) [37] [38] Colon cancer spheres (colon cancer) [39] Tissue-derived tumor spheres Colospheres [15] [20] Cancer tissue–originated spheroids [16] Spheroids [21] Organotypic multicellular spheroids Biopsy spheroids [85] Organotypic spheroids [177] Organotypic tumor spheroids [84] Fragment spheroids [50] Primary spheroids [178] Ovarian carcinoma ascites spheroids [48] Spherule [47] Neoplasia Vol. 17, No. 1, 2015 Cancer Spheres in Tumor Biology Weiswald et al. 3 More recently , several studies reported production of MCTSs using microcapsules with alginate - based membranes ( Figure 2 , G – H ) [ 56 , 57 ] . "
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    ABSTRACT: Three-dimensional (3D) in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.
    Full-text · Article · Jan 2015 · Neoplasia (New York, N.Y.)
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    • "The loss of TGFβ sensitivity in prostatic CAFs promoted PCa cell proliferation and invasion in a xenograft model [56]. Bone CAFs have increased levels of chemokine (C-C motif) ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL)5, versican, tenascin, connective tissue growth factor (CTGF), SDF-1, and hypoxia inducible factor 1-α (HIF-1α) [57]. "
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    ABSTRACT: The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients.
    Full-text · Article · May 2014 · BioMed Research International
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    • "The physiological role of the CXCL16/CXCR6 axis in cancer is unclear, with pro-metastatic as well as anti-tumorigenic functions being reported. In prostate cancer, high expression of CXCL16 and CXCR6 as well as high serum sCXCL16 levels were associated with a more aggressive tumour phenotype (Lu et al, 2008; Wang et al, 2008; Darash-Yahana et al, 2009) and increased formation of metastases (Hu et al, 2008; Sung et al, 2008; Ha et al, 2011). "
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    ABSTRACT: Background: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). Methods: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. Results: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29–4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. Conclusions: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours.
    Full-text · Article · Feb 2014 · British Journal of Cancer
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