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Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells
The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal can...
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| Published in: | Cancer research (Chicago, Ill.) Ill.), 2003-04, Vol.63 (8), p.1748-1751 |
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| creator | CUTLER, N. Shane GRAVES-DEAL, Ramona LAFLEUR, Bonnie J ZHENQIANG GAO BOMAN, Bruce M WHITEHEAD, Robert H TERRY, Erin MORROW, Jason D COFFEY, Robert J |
| description | The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal cancer (CRC) cell line, HCA-7, produces significant levels of PGE(2), PGD(2), thromboxane, and PGF(2alpha), but not PGI(2). We now report that human colonic fibroblast cell lines produce significant amounts of PGI(2) and that fibroblast lines derived from normal-appearing colonic mucosa of hereditary nonpolyposis CRC individuals produce 50-fold more PGI(2) than normal fibroblast lines derived from individuals with nonhereditary CRC. Coculture of HCA-7 cells with hereditary nonpolyposis CRC fibroblasts, but not normal fibroblasts, markedly reduced butyrate-induced apoptosis of HCA-7 cells. This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin. PGI(2) binds either G protein-coupled cell surface PGI(2) receptor or the nuclear peroxisome proliferator-activated receptor (PPAR) delta. PPAR delta likely mediates this antiapoptotic effect because HCA-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the effect. We propose a novel mechanism by which stromal production of PGI(2) promotes survival of colonocytes through PPAR delta activation. This mechanism may have relevance to maintenance of cells in the normal crypt and to clonal expansion of mutant colonocytes during tumorigenesis. |
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Shane ; GRAVES-DEAL, Ramona ; LAFLEUR, Bonnie J ; ZHENQIANG GAO ; BOMAN, Bruce M ; WHITEHEAD, Robert H ; TERRY, Erin ; MORROW, Jason D ; COFFEY, Robert J</creator><creatorcontrib>CUTLER, N. Shane ; GRAVES-DEAL, Ramona ; LAFLEUR, Bonnie J ; ZHENQIANG GAO ; BOMAN, Bruce M ; WHITEHEAD, Robert H ; TERRY, Erin ; MORROW, Jason D ; COFFEY, Robert J</creatorcontrib><description>The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal cancer (CRC) cell line, HCA-7, produces significant levels of PGE(2), PGD(2), thromboxane, and PGF(2alpha), but not PGI(2). We now report that human colonic fibroblast cell lines produce significant amounts of PGI(2) and that fibroblast lines derived from normal-appearing colonic mucosa of hereditary nonpolyposis CRC individuals produce 50-fold more PGI(2) than normal fibroblast lines derived from individuals with nonhereditary CRC. Coculture of HCA-7 cells with hereditary nonpolyposis CRC fibroblasts, but not normal fibroblasts, markedly reduced butyrate-induced apoptosis of HCA-7 cells. This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin. PGI(2) binds either G protein-coupled cell surface PGI(2) receptor or the nuclear peroxisome proliferator-activated receptor (PPAR) delta. PPAR delta likely mediates this antiapoptotic effect because HCA-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the effect. We propose a novel mechanism by which stromal production of PGI(2) promotes survival of colonocytes through PPAR delta activation. This mechanism may have relevance to maintenance of cells in the normal crypt and to clonal expansion of mutant colonocytes during tumorigenesis.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 12702555</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Apoptosis - physiology ; Biological and medical sciences ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Coculture Techniques ; Colon - cytology ; Colon - metabolism ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism ; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors - pharmacology ; Epithelial Cells - metabolism ; Epoprostenol - analogs & derivatives ; Epoprostenol - biosynthesis ; Fundamental and applied biological sciences. Psychology ; Humans ; Intestinal Mucosa - cytology ; Intestinal Mucosa - metabolism ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - metabolism ; Lactones - pharmacology ; Membrane Proteins ; Molecular and cellular biology ; Prostaglandin-Endoperoxide Synthases - metabolism ; Stromal Cells - metabolism ; Sulfones ; Tumor Cells, Cultured</subject><ispartof>Cancer research (Chicago, Ill.), 2003-04, Vol.63 (8), p.1748-1751</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14729228$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12702555$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CUTLER, N. Shane</creatorcontrib><creatorcontrib>GRAVES-DEAL, Ramona</creatorcontrib><creatorcontrib>LAFLEUR, Bonnie J</creatorcontrib><creatorcontrib>ZHENQIANG GAO</creatorcontrib><creatorcontrib>BOMAN, Bruce M</creatorcontrib><creatorcontrib>WHITEHEAD, Robert H</creatorcontrib><creatorcontrib>TERRY, Erin</creatorcontrib><creatorcontrib>MORROW, Jason D</creatorcontrib><creatorcontrib>COFFEY, Robert J</creatorcontrib><title>Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal cancer (CRC) cell line, HCA-7, produces significant levels of PGE(2), PGD(2), thromboxane, and PGF(2alpha), but not PGI(2). We now report that human colonic fibroblast cell lines produce significant amounts of PGI(2) and that fibroblast lines derived from normal-appearing colonic mucosa of hereditary nonpolyposis CRC individuals produce 50-fold more PGI(2) than normal fibroblast lines derived from individuals with nonhereditary CRC. Coculture of HCA-7 cells with hereditary nonpolyposis CRC fibroblasts, but not normal fibroblasts, markedly reduced butyrate-induced apoptosis of HCA-7 cells. This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin. PGI(2) binds either G protein-coupled cell surface PGI(2) receptor or the nuclear peroxisome proliferator-activated receptor (PPAR) delta. PPAR delta likely mediates this antiapoptotic effect because HCA-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the effect. We propose a novel mechanism by which stromal production of PGI(2) promotes survival of colonocytes through PPAR delta activation. This mechanism may have relevance to maintenance of cells in the normal crypt and to clonal expansion of mutant colonocytes during tumorigenesis.</description><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Coculture Techniques</subject><subject>Colon - cytology</subject><subject>Colon - metabolism</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - pathology</subject><subject>Cyclooxygenase 2</subject><subject>Cyclooxygenase 2 Inhibitors</subject><subject>Cyclooxygenase Inhibitors - pharmacology</subject><subject>Epithelial Cells - metabolism</subject><subject>Epoprostenol - analogs & derivatives</subject><subject>Epoprostenol - biosynthesis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Intestinal Mucosa - cytology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - metabolism</subject><subject>Lactones - pharmacology</subject><subject>Membrane Proteins</subject><subject>Molecular and cellular biology</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>Stromal Cells - metabolism</subject><subject>Sulfones</subject><subject>Tumor Cells, Cultured</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpFkE9LAzEQxYModq1-BdmLx4VsNmmSoxT_QcGDerVkJxMayW6WTXrotzfFSmFgeMOPx3tzQapWdKqRnItLUlFKVSO4ZAtyk9JPkaKl4posWiYpE0JU5Psjz3EwoZ7maPeQfRzr6I4qZQMHCH6sIY4O51SbsUz2ZopTjtlDjc4h5DrHgoQ4Hi-TzzsMvhgChpBuyZUzIeHdaS_J1_PT5_q12by_vK0fN82uJMkNWyluLSot27ZXWinTo0a54p2jnFkEzXXb95I5ANWh1R2ClSB0T6WmgnVLcv_nO-37Ae12mv1g5sP2v2gBHk6ASWCCm80IPp258iTNmOp-AUTQXwI</recordid><startdate>20030415</startdate><enddate>20030415</enddate><creator>CUTLER, N. Shane</creator><creator>GRAVES-DEAL, Ramona</creator><creator>LAFLEUR, Bonnie J</creator><creator>ZHENQIANG GAO</creator><creator>BOMAN, Bruce M</creator><creator>WHITEHEAD, Robert H</creator><creator>TERRY, Erin</creator><creator>MORROW, Jason D</creator><creator>COFFEY, Robert J</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></search><sort><creationdate>20030415</creationdate><title>Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells</title><author>CUTLER, N. Shane ; GRAVES-DEAL, Ramona ; LAFLEUR, Bonnie J ; ZHENQIANG GAO ; BOMAN, Bruce M ; WHITEHEAD, Robert H ; TERRY, Erin ; MORROW, Jason D ; COFFEY, Robert J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h270t-2684dde89711b8988abe9e7643f042dec9491bb72fcc83ed93ecd7c59b0790523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Coculture Techniques</topic><topic>Colon - cytology</topic><topic>Colon - metabolism</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - pathology</topic><topic>Cyclooxygenase 2</topic><topic>Cyclooxygenase 2 Inhibitors</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>Epithelial Cells - metabolism</topic><topic>Epoprostenol - analogs & derivatives</topic><topic>Epoprostenol - biosynthesis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Intestinal Mucosa - cytology</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - metabolism</topic><topic>Lactones - pharmacology</topic><topic>Membrane Proteins</topic><topic>Molecular and cellular biology</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>Stromal Cells - metabolism</topic><topic>Sulfones</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CUTLER, N. Shane</creatorcontrib><creatorcontrib>GRAVES-DEAL, Ramona</creatorcontrib><creatorcontrib>LAFLEUR, Bonnie J</creatorcontrib><creatorcontrib>ZHENQIANG GAO</creatorcontrib><creatorcontrib>BOMAN, Bruce M</creatorcontrib><creatorcontrib>WHITEHEAD, Robert H</creatorcontrib><creatorcontrib>TERRY, Erin</creatorcontrib><creatorcontrib>MORROW, Jason D</creatorcontrib><creatorcontrib>COFFEY, Robert J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CUTLER, N. Shane</au><au>GRAVES-DEAL, Ramona</au><au>LAFLEUR, Bonnie J</au><au>ZHENQIANG GAO</au><au>BOMAN, Bruce M</au><au>WHITEHEAD, Robert H</au><au>TERRY, Erin</au><au>MORROW, Jason D</au><au>COFFEY, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2003-04-15</date><risdate>2003</risdate><volume>63</volume><issue>8</issue><spage>1748</spage><epage>1751</epage><pages>1748-1751</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>The mechanism whereby cyclooxygenase-2 and its prostaglandin (PG) products are involved in colonic carcinogenesis is not fully understood. Prostacyclin (PGI(2)) is a major PG with antiapoptotic activity and is produced in the gastrointestinal tract. We reported previously that a human colorectal cancer (CRC) cell line, HCA-7, produces significant levels of PGE(2), PGD(2), thromboxane, and PGF(2alpha), but not PGI(2). We now report that human colonic fibroblast cell lines produce significant amounts of PGI(2) and that fibroblast lines derived from normal-appearing colonic mucosa of hereditary nonpolyposis CRC individuals produce 50-fold more PGI(2) than normal fibroblast lines derived from individuals with nonhereditary CRC. Coculture of HCA-7 cells with hereditary nonpolyposis CRC fibroblasts, but not normal fibroblasts, markedly reduced butyrate-induced apoptosis of HCA-7 cells. This antiapoptotic effect was inhibited by the cyclooxygenase-2 inhibitor rofecoxib and was restored by the stable PGI(2) analogue carbaprostacyclin. PGI(2) binds either G protein-coupled cell surface PGI(2) receptor or the nuclear peroxisome proliferator-activated receptor (PPAR) delta. PPAR delta likely mediates this antiapoptotic effect because HCA-7 cells express this receptor, and another PPAR delta agonist, docosahexaenoic acid, mimics the effect. We propose a novel mechanism by which stromal production of PGI(2) promotes survival of colonocytes through PPAR delta activation. This mechanism may have relevance to maintenance of cells in the normal crypt and to clonal expansion of mutant colonocytes during tumorigenesis.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>12702555</pmid><tpages>4</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2003-04, Vol.63 (8), p.1748-1751 |
| issn | 0008-5472 1538-7445 |
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| subjects | Apoptosis - physiology Biological and medical sciences Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Coculture Techniques Colon - cytology Colon - metabolism Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism Colorectal Neoplasms, Hereditary Nonpolyposis - pathology Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors - pharmacology Epithelial Cells - metabolism Epoprostenol - analogs & derivatives Epoprostenol - biosynthesis Fundamental and applied biological sciences. Psychology Humans Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Isoenzymes - antagonists & inhibitors Isoenzymes - metabolism Lactones - pharmacology Membrane Proteins Molecular and cellular biology Prostaglandin-Endoperoxide Synthases - metabolism Stromal Cells - metabolism Sulfones Tumor Cells, Cultured |
| title | Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells |
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