Cancer-Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer.

Microarrays Pub Date : 2015-10-29 DOI:10.3390/microarrays4040503

Aimy Sebastian, Nicholas R Hum, Bryan D Hudson, Gabriela G Loots

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引用次数: 33

Abstract

Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study, we utilized an in vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer-bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (Sost(KO)) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-Sost(KO) osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with Sost(KO) osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer.

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前列腺癌与成骨细胞相互作用降低成骨细胞中Sost的表达并上调lncRNA MALAT1。

前列腺癌与骨微环境之间的动态相互作用是前列腺癌向骨转移的主要因素。在这项研究中，我们利用PC3前列腺癌细胞和成骨细胞的体外共培养模型，然后利用基于微阵列的基因表达谱来鉴定以前未被识别的前列腺癌-骨微环境相互作用。PC3细胞分泌的因子导致成骨细胞中Mmp13、Il-6、Tgfb2等骨代谢和肿瘤转移相关基因上调，Wnt抑制剂Sost下调。为了确定骨微环境中Sost表达的改变是否对前列腺癌转移有影响，我们将PC3细胞与Sost敲除(Sost(KO))成骨细胞和野生型(WT)成骨细胞共培养，并鉴定了PC3-Sost(KO)成骨细胞共培养和PC3-WT成骨细胞共培养之间的几个差异调控基因。PC3细胞与WT成骨细胞共培养可上调PC3细胞中癌症相关的长链非编码RNA (lncRNA) MALAT1。当PC3细胞与Sost(KO)成骨细胞共培养时，MALAT1的表达进一步增强，重组Sost处理可下调这些细胞中MALAT1的表达。我们的研究结果表明，在前列腺癌中，肿瘤微环境中Sost表达的降低可能通过上调MALAT1来促进骨转移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microarrays

自引率

0.00%

发文量

审稿时长

11 weeks

期刊介绍： High-Throughput (formerly Microarrays, ISSN 2076-3905) is a multidisciplinary peer-reviewed scientific journal that provides an advanced forum for the publication of studies reporting high-dimensional approaches and developments in Life Sciences, Chemistry and related fields. Our aim is to encourage scientists to publish their experimental and theoretical results based on high-throughput techniques as well as computational and statistical tools for data analysis and interpretation. The full experimental or methodological details must be provided so that the results can be reproduced. There is no restriction on the length of the papers. High-Throughput invites submissions covering several topics, including, but not limited to: Microarrays, DNA Sequencing, RNA Sequencing, Protein Identification and Quantification, Cell-based Approaches, Omics Technologies, Imaging, Bioinformatics, Computational Biology/Chemistry, Statistics, Integrative Omics, Drug Discovery and Development, Microfluidics, Lab-on-a-chip, Data Mining, Databases, Multiplex Assays.