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Cell Journal، جلد ۱۷، شماره Suppl ۱، صفحات ۹-۹
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عنوان انگلیسی Is-2: Role of Extracellular Matrix Proteins in Cancer Cell Dormancy within Prostate Cancer Draining Lymph Nodes
چکیده انگلیسی مقاله Objective: Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. We wanted to investigate this issue in a pre-clinical model of prostate cancer. Materials and Methods: Utilizing the sphere assay, we established long-term prostate cancer stem-like/progenitor cell (CSC) lines from unsorted prostate or prostate draining lymph node cells obtained from different stages of prostate cancer progression in transgenic adenocarcinoma of the mouse (TRAMP). CSCs lines were assessed in vitro and in vivo for immunosuppressive activities. Results: CSCs were found in histopathologically negative prostate draining lymph nodes in TRAMP mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). Prostate draining lymph node-derived CSCs were phenotypically and functionally identical to CSCs obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. These CSCs blocked T cell functions in vitro and in vivo through several mechanisms, including the release of extracellular matrix proteins like Tenascin C (TNC) and Galectin-3 (Gal-3). CSCs from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in prostate draining lymph nodes upon mPIN development. CXCR4 was critical for the development of prostate draining lymph node-derived CSCs, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Conclusion: Taken together, our work establishes a pivotal role for TNC and other factors released form CSCs in fine-tuning the local immune response to establish equilibrium between disseminated nodal CSCs and the immune system.
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نویسندگان مقاله m bellone | m bellone


نشانی اینترنتی http://celljournal.org/journal/article/abstract/26
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