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Open AccessArticle

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

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Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA
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School of Natural Sciences, University of California, Merced, CA 95343, USA
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Author to whom correspondence should be addressed.
Academic Editor: Xin Ma
Microarrays 2015, 4(4), 503-519; https://doi.org/10.3390/microarrays4040503
Received: 15 September 2015 / Revised: 17 October 2015 / Accepted: 22 October 2015 / Published: 29 October 2015
(This article belongs to the Special Issue Microarray Gene Expression Data Analysis)
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 (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO 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 SostKO 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. View Full-Text
Keywords: prostate cancer; osteoblast; MALAT1; Sost; co-culture; Mmp13; Il6; Tgfb2; PC3 prostate cancer; osteoblast; MALAT1; Sost; co-culture; Mmp13; Il6; Tgfb2; PC3
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Sebastian, A.; Hum, N.R.; Hudson, B.D.; Loots, G.G. Cancer–Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer. Microarrays 2015, 4, 503-519.

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