RESUMEN
BACKGROUND: RECK is a tumor suppressor which inhibits metastasis and angiogenesis. Based on RECK expression in prostate cancer tissue and cell lines, our aim was to investigate functional relevance of RECK for prostate carcinoma. METHODS: RECK protein levels were determined by Western blotting in the human prostate cell lines BPH-1, DU-145, LNCaP, PC-3, and in tissue of 12 normal/tumor matches of patients after radical prostatectomy. Functional characteristics of DU-145 cells with stable RECK overexpression included proliferation, invasion, regulation of matrix metalloproteinases MMP-2, MMP-9, and MMP-14 measured by zymography (MMP-2 and -9) or commercially available assays. RESULTS: RECK was expressed in cell lines and tissue with a significant decrease in malignant tissue (P = 0.002). RECK overexpression caused an up to 80% decrease in invasion for DU-145 cells (P < 0.001) and a decrease of pro-MMP-9 (42%) and of pro-/active MMP-14 (up to 53% of control). Proliferation was not affected by RECK overexpression. CONCLUSIONS: The considerable anti-invasive potential of RECK points to new therapeutic possibilities for prostate cancer.
Asunto(s)
Proteínas Ligadas a GPI/biosíntesis , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Regulación hacia Abajo/genética , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/fisiología , Humanos , Masculino , Invasividad Neoplásica/prevención & control , Neoplasias de la Próstata/genéticaRESUMEN
The selection of pluripotent stem cell (PSC)-derived cells for tissue modeling and cell therapy will be influenced by their response to the tissue environment, including the extracellular matrix (ECM). Whether and how instructive memory is imprinted in adult ECM and able to impact on the tissue specific determination of human PSC-derived developmentally fetal mesodermal precursor (P-meso) cells is investigated. Decellularized ECM (dECM) is generated from human heart, kidney, and lung tissues and recellularized with P-meso cells in a medium not containing any differentiation inducing components. While P-meso cells on kidney dECM differentiate exclusively into nephronal cells, only beating clusters containing mature and immature cardiac cells form on heart dECM. No tissue-specific differentiation of P-meso cells is observed on endoderm-derived lung dECM. P-meso-derived endothelial cells, however, are found on all dECM preparations independent of tissue origin. Clearance of heparan-sulfate proteoglycans (HSPG) from dECM abolishes induction of tissue-specific differentiation. It is concluded that HSPG-bound factors on adult tissue-derived ECM are essential and sufficient to induce tissue-specific specification of uncommitted fetal stage precursor cells.