p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner
The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Sp...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2010-12, Vol.70 (23), p.9650-9658 |
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| creator | ADDADI, Yoseph MOSKOVITS, Neta GRANOT, Dorit LOZANO, Guillermina CARMI, Yaron APTE, Ron N NEEMAN, Michal OREN, Moshe |
| description | The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell nonautonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development. |
| doi_str_mv | 10.1158/0008-5472.can-10-1146 |
| format | Article |
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In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell nonautonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-10-1146</identifier><identifier>PMID: 20952507</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Biological and medical sciences ; Cell Line, Tumor ; Cells, Cultured ; Chemokine CXCL12 - genetics ; Chemokine CXCL12 - metabolism ; Embryo, Mammalian - cytology ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Humans ; Immunoblotting ; Luciferases - genetics ; Luciferases - metabolism ; Luminescent Measurements - methods ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, SCID ; Mutation ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; Pharmacology. Drug treatments ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Stromal Cells - metabolism ; Transplantation, Heterologous ; Tumor Burden ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2010-12, Vol.70 (23), p.9650-9658</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-b79aefc530bac2a95c72c7b84c673c79a306d2d6120695a1ba93cd2eceaa17943</citedby><cites>FETCH-LOGICAL-c538t-b79aefc530bac2a95c72c7b84c673c79a306d2d6120695a1ba93cd2eceaa17943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,3357,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23620059$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20952507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ADDADI, Yoseph</creatorcontrib><creatorcontrib>MOSKOVITS, Neta</creatorcontrib><creatorcontrib>GRANOT, Dorit</creatorcontrib><creatorcontrib>LOZANO, Guillermina</creatorcontrib><creatorcontrib>CARMI, Yaron</creatorcontrib><creatorcontrib>APTE, Ron N</creatorcontrib><creatorcontrib>NEEMAN, Michal</creatorcontrib><creatorcontrib>OREN, Moshe</creatorcontrib><title>p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell nonautonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cells, Cultured</subject><subject>Chemokine CXCL12 - genetics</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Embryo, Mammalian - cytology</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>Luminescent Measurements - methods</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, SCID</subject><subject>Mutation</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Stromal Cells - metabolism</subject><subject>Transplantation, Heterologous</subject><subject>Tumor Burden</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u2zAQhImgQe24fYQEuhQ5yeGPSIqXAIZduwWS5hD3TKwoulYgkQ4ppejbh4ZdNzn1xCX3m8EQg9AlwVNCeHmDMS5zXkg6NeBygnNCCnGGxoSzMpdFwT-g8YkZoYsYn9KVE8w_ohHFilOO5Ritd5xljz30Q8wal6bgO2izZVMFX7UQ-5jd-3poobcxWw-dD9kq-N_9dk9DEiyWJF_YnXW1dX12D87Z8Amdb6CN9vPxnKCfy6_r-bf87mH1fT67y00K2eeVVGA3acYVGAqKG0mNrMrCCMlMWjIsaloLQrFQHEgFipmaWmMBiFQFm6Dbg-9uqDpbm5QgQKt3oekg_NEeGv1-45qt_uVfNFVKCc6SwfXRIPjnwcZed000tm3BWT9ErbAkhRJU_ZcsiZAq5SSJ5AfSBB9jsJtTHoL1vjq9r0Xva9Hz2Y_DayGS7urtZ06qv10l4MsRgGig3QRwpon_OCZoKlixV97loj4</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>ADDADI, Yoseph</creator><creator>MOSKOVITS, Neta</creator><creator>GRANOT, Dorit</creator><creator>LOZANO, Guillermina</creator><creator>CARMI, Yaron</creator><creator>APTE, Ron N</creator><creator>NEEMAN, Michal</creator><creator>OREN, Moshe</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><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>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20101201</creationdate><title>p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner</title><author>ADDADI, Yoseph ; MOSKOVITS, Neta ; GRANOT, Dorit ; LOZANO, Guillermina ; CARMI, Yaron ; APTE, Ron N ; NEEMAN, Michal ; OREN, Moshe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-b79aefc530bac2a95c72c7b84c673c79a306d2d6120695a1ba93cd2eceaa17943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cells, Cultured</topic><topic>Chemokine CXCL12 - genetics</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Embryo, Mammalian - cytology</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Luciferases - genetics</topic><topic>Luciferases - metabolism</topic><topic>Luminescent Measurements - methods</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, SCID</topic><topic>Mutation</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Stromal Cells - metabolism</topic><topic>Transplantation, Heterologous</topic><topic>Tumor Burden</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ADDADI, Yoseph</creatorcontrib><creatorcontrib>MOSKOVITS, Neta</creatorcontrib><creatorcontrib>GRANOT, Dorit</creatorcontrib><creatorcontrib>LOZANO, Guillermina</creatorcontrib><creatorcontrib>CARMI, Yaron</creatorcontrib><creatorcontrib>APTE, Ron N</creatorcontrib><creatorcontrib>NEEMAN, Michal</creatorcontrib><creatorcontrib>OREN, Moshe</creatorcontrib><collection>Pascal-Francis</collection><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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ADDADI, Yoseph</au><au>MOSKOVITS, Neta</au><au>GRANOT, Dorit</au><au>LOZANO, Guillermina</au><au>CARMI, Yaron</au><au>APTE, Ron N</au><au>NEEMAN, Michal</au><au>OREN, Moshe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>70</volume><issue>23</issue><spage>9650</spage><epage>9658</epage><pages>9650-9658</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>The p53 tumor suppressor exerts a variety of cell-autonomous effects that are aimed to thwart tumor development. In addition, however, there is growing evidence for cell nonautonomous tumor suppressor effects of p53. In the present study, we investigated the impact of stromal p53 on tumor growth. Specifically, we found that ablation of p53 in fibroblasts enabled them to promote more efficiently the growth of tumors initiated by PC3 prostate cancer-derived cells. This stimulatory effect was dependent on the increased expression of the chemokine SDF-1 in the p53-deficient fibroblasts. Notably, fibroblasts harboring mutant p53 protein were more effective than p53-null fibroblasts in promoting tumor growth. The presence of either p53-null or p53-mutant fibroblasts led also to a markedly elevated rate of metastatic spread of the PC3 tumors. These findings implicate p53 in a cell nonautonomous tumor suppressor role within stromal fibroblasts, through suppressing the production of tumor stimulatory factors by these cells. Moreover, expression of mutant p53 by tumor stroma fibroblasts might exert a gain of function effect, further accelerating tumor development.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>20952507</pmid><doi>10.1158/0008-5472.can-10-1146</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic agents Biological and medical sciences Cell Line, Tumor Cells, Cultured Chemokine CXCL12 - genetics Chemokine CXCL12 - metabolism Embryo, Mammalian - cytology Fibroblasts - cytology Fibroblasts - metabolism Humans Immunoblotting Luciferases - genetics Luciferases - metabolism Luminescent Measurements - methods Male Medical sciences Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID Mutation Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Neoplasms, Experimental - pathology Pharmacology. Drug treatments Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Reverse Transcriptase Polymerase Chain Reaction Stromal Cells - metabolism Transplantation, Heterologous Tumor Burden Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors |
| title | p53 Status in Stromal Fibroblasts Modulates Tumor Growth in an SDF1-Dependent Manner |
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