Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis
•AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs. Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerat...
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creator | Takahara, Kiyoshi Ii, Masaaki Inamoto, Teruo Komura, Kazumasa Ibuki, Naokazu Minami, Koichiro Uehara, Hirofumi Hirano, Hajime Nomi, Hayahito Kiyama, Satoshi Asahi, Michio Azuma, Haruhito |
description | •AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs.
Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa. |
doi_str_mv | 10.1016/j.bbrc.2014.03.080 |
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Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2014.03.080</identifier><identifier>PMID: 24680678</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADIPOSE TISSUE ; Adipose Tissue - cytology ; AdSCs ; ANDROGENS ; Animals ; APOPTOSIS ; BONE MARROW ; Cell Line, Tumor ; CELL PROLIFERATION ; DRUGS ; FIBROBLASTS ; GENES ; HUMAN POPULATIONS ; Humans ; IN VITRO ; Male ; MICE ; NEOPLASMS ; PATIENTS ; PCa ; PROSTATE ; Prostate - metabolism ; Prostate - pathology ; Prostate cancer ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - therapy ; Signal Transduction ; Stem cell ; STEM CELLS ; Stromal Cells - cytology ; Stromal Cells - metabolism ; Stromal Cells - transplantation ; THERAPY ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism ; Up-Regulation</subject><ispartof>Biochemical and biophysical research communications, 2014-04, Vol.446 (4), p.1102-1107</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-c04adb81a9173211ee9c4f9e12579e2cfa71b34ad4ec0a30293b1b816c17d23e3</citedby><cites>FETCH-LOGICAL-c450t-c04adb81a9173211ee9c4f9e12579e2cfa71b34ad4ec0a30293b1b816c17d23e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X14005233$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24680678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22416387$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Takahara, Kiyoshi</creatorcontrib><creatorcontrib>Ii, Masaaki</creatorcontrib><creatorcontrib>Inamoto, Teruo</creatorcontrib><creatorcontrib>Komura, Kazumasa</creatorcontrib><creatorcontrib>Ibuki, Naokazu</creatorcontrib><creatorcontrib>Minami, Koichiro</creatorcontrib><creatorcontrib>Uehara, Hirofumi</creatorcontrib><creatorcontrib>Hirano, Hajime</creatorcontrib><creatorcontrib>Nomi, Hayahito</creatorcontrib><creatorcontrib>Kiyama, Satoshi</creatorcontrib><creatorcontrib>Asahi, Michio</creatorcontrib><creatorcontrib>Azuma, Haruhito</creatorcontrib><title>Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>•AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs.
Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADIPOSE TISSUE</subject><subject>Adipose Tissue - cytology</subject><subject>AdSCs</subject><subject>ANDROGENS</subject><subject>Animals</subject><subject>APOPTOSIS</subject><subject>BONE MARROW</subject><subject>Cell Line, Tumor</subject><subject>CELL PROLIFERATION</subject><subject>DRUGS</subject><subject>FIBROBLASTS</subject><subject>GENES</subject><subject>HUMAN POPULATIONS</subject><subject>Humans</subject><subject>IN VITRO</subject><subject>Male</subject><subject>MICE</subject><subject>NEOPLASMS</subject><subject>PATIENTS</subject><subject>PCa</subject><subject>PROSTATE</subject><subject>Prostate - metabolism</subject><subject>Prostate - pathology</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Signal Transduction</subject><subject>Stem cell</subject><subject>STEM CELLS</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - metabolism</subject><subject>Stromal Cells - transplantation</subject><subject>THERAPY</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Up-Regulation</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpabZJ_0AOwdBLL3ZnJK1tQS5hST8g0EsLhRyELI0bLV7LlbSB_vvK3TTHngSjZ17eeRi7RGgQsP2wb4Yh2oYDygZEAz28YBsEBTVHkC_ZBgDamiv8ccbepLQHQJStes3OuGx7aLt-w-5vnF9CotpR9I_kqpRjOJipsjRNqfLzgx98rpYYUjaZKmtmS_Hv7zqc_EjRZB_mgrqj9fPPyixhySH5dMFejWZK9PbpPWffP95-232u775--rK7uaut3EKuLUjjhh6Nwk5wRCJl5agI-bZTxO1oOhxEYSRZMAK4EgMWvrXYOS5InLN3p9zS0etkfSb7YMM8k82ac4mt6LtCvT9RpfavI6WsDz6td5iZwjFp3KLiLfSyLyg_obacnSKNeon-YOJvjaBX9XqvV_V6Va9B6KK-LF095R-HA7nnlX-uC3B9Aqi4ePQU16pUdDof16Yu-P_l_wEQyZW4</recordid><startdate>20140418</startdate><enddate>20140418</enddate><creator>Takahara, Kiyoshi</creator><creator>Ii, Masaaki</creator><creator>Inamoto, Teruo</creator><creator>Komura, Kazumasa</creator><creator>Ibuki, Naokazu</creator><creator>Minami, Koichiro</creator><creator>Uehara, Hirofumi</creator><creator>Hirano, Hajime</creator><creator>Nomi, Hayahito</creator><creator>Kiyama, Satoshi</creator><creator>Asahi, Michio</creator><creator>Azuma, Haruhito</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20140418</creationdate><title>Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis</title><author>Takahara, Kiyoshi ; Ii, Masaaki ; Inamoto, Teruo ; Komura, Kazumasa ; Ibuki, Naokazu ; Minami, Koichiro ; Uehara, Hirofumi ; Hirano, Hajime ; Nomi, Hayahito ; Kiyama, Satoshi ; Asahi, Michio ; Azuma, Haruhito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-c04adb81a9173211ee9c4f9e12579e2cfa71b34ad4ec0a30293b1b816c17d23e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADIPOSE TISSUE</topic><topic>Adipose Tissue - cytology</topic><topic>AdSCs</topic><topic>ANDROGENS</topic><topic>Animals</topic><topic>APOPTOSIS</topic><topic>BONE MARROW</topic><topic>Cell Line, Tumor</topic><topic>CELL PROLIFERATION</topic><topic>DRUGS</topic><topic>FIBROBLASTS</topic><topic>GENES</topic><topic>HUMAN POPULATIONS</topic><topic>Humans</topic><topic>IN VITRO</topic><topic>Male</topic><topic>MICE</topic><topic>NEOPLASMS</topic><topic>PATIENTS</topic><topic>PCa</topic><topic>PROSTATE</topic><topic>Prostate - metabolism</topic><topic>Prostate - pathology</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Signal Transduction</topic><topic>Stem cell</topic><topic>STEM CELLS</topic><topic>Stromal Cells - cytology</topic><topic>Stromal Cells - metabolism</topic><topic>Stromal Cells - transplantation</topic><topic>THERAPY</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takahara, Kiyoshi</creatorcontrib><creatorcontrib>Ii, Masaaki</creatorcontrib><creatorcontrib>Inamoto, Teruo</creatorcontrib><creatorcontrib>Komura, Kazumasa</creatorcontrib><creatorcontrib>Ibuki, Naokazu</creatorcontrib><creatorcontrib>Minami, Koichiro</creatorcontrib><creatorcontrib>Uehara, Hirofumi</creatorcontrib><creatorcontrib>Hirano, Hajime</creatorcontrib><creatorcontrib>Nomi, Hayahito</creatorcontrib><creatorcontrib>Kiyama, Satoshi</creatorcontrib><creatorcontrib>Asahi, Michio</creatorcontrib><creatorcontrib>Azuma, Haruhito</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takahara, Kiyoshi</au><au>Ii, Masaaki</au><au>Inamoto, Teruo</au><au>Komura, Kazumasa</au><au>Ibuki, Naokazu</au><au>Minami, Koichiro</au><au>Uehara, Hirofumi</au><au>Hirano, Hajime</au><au>Nomi, Hayahito</au><au>Kiyama, Satoshi</au><au>Asahi, Michio</au><au>Azuma, Haruhito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2014-04-18</date><risdate>2014</risdate><volume>446</volume><issue>4</issue><spage>1102</spage><epage>1107</epage><pages>1102-1107</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>•AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells.•AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway.•High expression of the TGF-β1 gene in AdSCs.
Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24680678</pmid><doi>10.1016/j.bbrc.2014.03.080</doi><tpages>6</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES ADIPOSE TISSUE Adipose Tissue - cytology AdSCs ANDROGENS Animals APOPTOSIS BONE MARROW Cell Line, Tumor CELL PROLIFERATION DRUGS FIBROBLASTS GENES HUMAN POPULATIONS Humans IN VITRO Male MICE NEOPLASMS PATIENTS PCa PROSTATE Prostate - metabolism Prostate - pathology Prostate cancer Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Prostatic Neoplasms - therapy Signal Transduction Stem cell STEM CELLS Stromal Cells - cytology Stromal Cells - metabolism Stromal Cells - transplantation THERAPY Transforming Growth Factor beta - genetics Transforming Growth Factor beta - metabolism Up-Regulation |
title | Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis |
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