Loading…
Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis
Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) and ; mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumo...
Saved in:
| Published in: | Cancer research (Chicago, Ill.) Ill.), 2017-05, Vol.77 (10), p.2620-2632 |
|---|---|
| Main Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3 |
| container_end_page | 2632 |
| container_issue | 10 |
| container_start_page | 2620 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 77 |
| creator | Tomkovich, Sarah Yang, Ye Winglee, Kathryn Gauthier, Josee Mühlbauer, Marcus Sun, Xiaolun Mohamadzadeh, Mansour Liu, Xiuli Martin, Patricia Wang, Gary P Oswald, Eric Fodor, Anthony A Jobin, Christian |
| description | Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF)
and
;
mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed
;
, but not in
mice. In contrast, small intestinal neoplasia development significantly correlated with age in both
;
and
mice. GF
;
mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while
clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis,
promoted tumorigenesis in the
;
model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.
. |
| doi_str_mv | 10.1158/0008-5472.can-16-3472 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5468752</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1889386826</sourcerecordid><originalsourceid>FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3</originalsourceid><addsrcrecordid>eNqFkktP3DAUhS3UCgbanwCK1E1ZBPy2s0EaRTwqDdBK7dryODeDUcYGO4PUf19HQ0ctG1Z-fefcK5-L0DHBZ4QIfY4x1rXgip45G2oia1b2e2hGBNO14lx8QLMdc4AOc34sR0Gw2EcHVHMieUNm6Mciuphg5WOwQ3XZ9-DGXMW-uvUuxaWPo618qGz1PYEbfPCuYLexg2GC2jjEULU2OR_iCgJknz-hj70dMnx-XY_Qr6vLn-1Nvbi__tbOF7WTSo6l44ZTCry3jPcaS1BSqiVgsM4KprACYTvaKaWc7YW1ILpGSyCNWGpWGHaELra-T5vlGjoHYUx2ME_Jr236baL15v-X4B_MKr4YwaVWghaD063BwxvZzXxhpjtMJFZU0RdS2K-vxVJ83kAezdpnB8NgA8RNNqTBkktCtXgf1bphWmoqC_rlDfoYN6kEMRlqRkVDyVRbbKkSSM4J-l2zBJtpFsyUs5lyNu38zhBpplkoupN_P2in-hs--wNUG68v</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983259211</pqid></control><display><type>article</type><title>Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis</title><source>EZB Electronic Journals Library</source><creator>Tomkovich, Sarah ; Yang, Ye ; Winglee, Kathryn ; Gauthier, Josee ; Mühlbauer, Marcus ; Sun, Xiaolun ; Mohamadzadeh, Mansour ; Liu, Xiuli ; Martin, Patricia ; Wang, Gary P ; Oswald, Eric ; Fodor, Anthony A ; Jobin, Christian</creator><creatorcontrib>Tomkovich, Sarah ; Yang, Ye ; Winglee, Kathryn ; Gauthier, Josee ; Mühlbauer, Marcus ; Sun, Xiaolun ; Mohamadzadeh, Mansour ; Liu, Xiuli ; Martin, Patricia ; Wang, Gary P ; Oswald, Eric ; Fodor, Anthony A ; Jobin, Christian</creatorcontrib><description>Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF)
and
;
mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed
;
, but not in
mice. In contrast, small intestinal neoplasia development significantly correlated with age in both
;
and
mice. GF
;
mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while
clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis,
promoted tumorigenesis in the
;
model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.
.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-16-3472</identifier><identifier>PMID: 28416491</identifier><language>eng</language><publisher>United States: American Association for Cancer Research, Inc</publisher><subject>Adenomatous Polyposis Coli Protein - deficiency ; Adhesins ; Age ; Animals ; Bacteria ; Bacteria - classification ; Bacteria - genetics ; Cancer ; Carcinogenesis ; Cell Transformation, Neoplastic ; Clinical isolates ; Colon ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - etiology ; Colorectal Neoplasms - pathology ; Disease Models, Animal ; Etiology ; Fusobacterium nucleatum ; Gastrointestinal Microbiome ; Germfree ; Gnotobiotic ; Human health and pathology ; Hépatology and Gastroenterology ; Inflammation ; Inflammation - complications ; Inflammation - pathology ; Interleukin 1 ; Interleukin 10 ; Interleukin-10 - deficiency ; Large intestine ; Life Sciences ; Mice ; Mice, Knockout ; Mice, Transgenic ; Microbiomes ; Microbiota ; Small intestine ; Specific pathogen free ; Tumorigenesis ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 2017-05, Vol.77 (10), p.2620-2632</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research, Inc. May 15, 2017</rights><rights>Attribution - ShareAlike</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3</citedby><cites>FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3</cites><orcidid>0000-0002-3662-3846</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28416491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01607272$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomkovich, Sarah</creatorcontrib><creatorcontrib>Yang, Ye</creatorcontrib><creatorcontrib>Winglee, Kathryn</creatorcontrib><creatorcontrib>Gauthier, Josee</creatorcontrib><creatorcontrib>Mühlbauer, Marcus</creatorcontrib><creatorcontrib>Sun, Xiaolun</creatorcontrib><creatorcontrib>Mohamadzadeh, Mansour</creatorcontrib><creatorcontrib>Liu, Xiuli</creatorcontrib><creatorcontrib>Martin, Patricia</creatorcontrib><creatorcontrib>Wang, Gary P</creatorcontrib><creatorcontrib>Oswald, Eric</creatorcontrib><creatorcontrib>Fodor, Anthony A</creatorcontrib><creatorcontrib>Jobin, Christian</creatorcontrib><title>Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF)
and
;
mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed
;
, but not in
mice. In contrast, small intestinal neoplasia development significantly correlated with age in both
;
and
mice. GF
;
mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while
clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis,
promoted tumorigenesis in the
;
model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.
.</description><subject>Adenomatous Polyposis Coli Protein - deficiency</subject><subject>Adhesins</subject><subject>Age</subject><subject>Animals</subject><subject>Bacteria</subject><subject>Bacteria - classification</subject><subject>Bacteria - genetics</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Cell Transformation, Neoplastic</subject><subject>Clinical isolates</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - etiology</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Disease Models, Animal</subject><subject>Etiology</subject><subject>Fusobacterium nucleatum</subject><subject>Gastrointestinal Microbiome</subject><subject>Germfree</subject><subject>Gnotobiotic</subject><subject>Human health and pathology</subject><subject>Hépatology and Gastroenterology</subject><subject>Inflammation</subject><subject>Inflammation - complications</subject><subject>Inflammation - pathology</subject><subject>Interleukin 1</subject><subject>Interleukin 10</subject><subject>Interleukin-10 - deficiency</subject><subject>Large intestine</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Small intestine</subject><subject>Specific pathogen free</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFkktP3DAUhS3UCgbanwCK1E1ZBPy2s0EaRTwqDdBK7dryODeDUcYGO4PUf19HQ0ctG1Z-fefcK5-L0DHBZ4QIfY4x1rXgip45G2oia1b2e2hGBNO14lx8QLMdc4AOc34sR0Gw2EcHVHMieUNm6Mciuphg5WOwQ3XZ9-DGXMW-uvUuxaWPo618qGz1PYEbfPCuYLexg2GC2jjEULU2OR_iCgJknz-hj70dMnx-XY_Qr6vLn-1Nvbi__tbOF7WTSo6l44ZTCry3jPcaS1BSqiVgsM4KprACYTvaKaWc7YW1ILpGSyCNWGpWGHaELra-T5vlGjoHYUx2ME_Jr236baL15v-X4B_MKr4YwaVWghaD063BwxvZzXxhpjtMJFZU0RdS2K-vxVJ83kAezdpnB8NgA8RNNqTBkktCtXgf1bphWmoqC_rlDfoYN6kEMRlqRkVDyVRbbKkSSM4J-l2zBJtpFsyUs5lyNu38zhBpplkoupN_P2in-hs--wNUG68v</recordid><startdate>20170515</startdate><enddate>20170515</enddate><creator>Tomkovich, Sarah</creator><creator>Yang, Ye</creator><creator>Winglee, Kathryn</creator><creator>Gauthier, Josee</creator><creator>Mühlbauer, Marcus</creator><creator>Sun, Xiaolun</creator><creator>Mohamadzadeh, Mansour</creator><creator>Liu, Xiuli</creator><creator>Martin, Patricia</creator><creator>Wang, Gary P</creator><creator>Oswald, Eric</creator><creator>Fodor, Anthony A</creator><creator>Jobin, Christian</creator><general>American Association for Cancer Research, Inc</general><general>American Association for Cancer Research</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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3662-3846</orcidid></search><sort><creationdate>20170515</creationdate><title>Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis</title><author>Tomkovich, Sarah ; Yang, Ye ; Winglee, Kathryn ; Gauthier, Josee ; Mühlbauer, Marcus ; Sun, Xiaolun ; Mohamadzadeh, Mansour ; Liu, Xiuli ; Martin, Patricia ; Wang, Gary P ; Oswald, Eric ; Fodor, Anthony A ; Jobin, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenomatous Polyposis Coli Protein - deficiency</topic><topic>Adhesins</topic><topic>Age</topic><topic>Animals</topic><topic>Bacteria</topic><topic>Bacteria - classification</topic><topic>Bacteria - genetics</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Cell Transformation, Neoplastic</topic><topic>Clinical isolates</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - etiology</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Disease Models, Animal</topic><topic>Etiology</topic><topic>Fusobacterium nucleatum</topic><topic>Gastrointestinal Microbiome</topic><topic>Germfree</topic><topic>Gnotobiotic</topic><topic>Human health and pathology</topic><topic>Hépatology and Gastroenterology</topic><topic>Inflammation</topic><topic>Inflammation - complications</topic><topic>Inflammation - pathology</topic><topic>Interleukin 1</topic><topic>Interleukin 10</topic><topic>Interleukin-10 - deficiency</topic><topic>Large intestine</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Small intestine</topic><topic>Specific pathogen free</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomkovich, Sarah</creatorcontrib><creatorcontrib>Yang, Ye</creatorcontrib><creatorcontrib>Winglee, Kathryn</creatorcontrib><creatorcontrib>Gauthier, Josee</creatorcontrib><creatorcontrib>Mühlbauer, Marcus</creatorcontrib><creatorcontrib>Sun, Xiaolun</creatorcontrib><creatorcontrib>Mohamadzadeh, Mansour</creatorcontrib><creatorcontrib>Liu, Xiuli</creatorcontrib><creatorcontrib>Martin, Patricia</creatorcontrib><creatorcontrib>Wang, Gary P</creatorcontrib><creatorcontrib>Oswald, Eric</creatorcontrib><creatorcontrib>Fodor, Anthony A</creatorcontrib><creatorcontrib>Jobin, Christian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</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>Tomkovich, Sarah</au><au>Yang, Ye</au><au>Winglee, Kathryn</au><au>Gauthier, Josee</au><au>Mühlbauer, Marcus</au><au>Sun, Xiaolun</au><au>Mohamadzadeh, Mansour</au><au>Liu, Xiuli</au><au>Martin, Patricia</au><au>Wang, Gary P</au><au>Oswald, Eric</au><au>Fodor, Anthony A</au><au>Jobin, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2017-05-15</date><risdate>2017</risdate><volume>77</volume><issue>10</issue><spage>2620</spage><epage>2632</epage><pages>2620-2632</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><abstract>Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF)
and
;
mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed
;
, but not in
mice. In contrast, small intestinal neoplasia development significantly correlated with age in both
;
and
mice. GF
;
mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while
clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis,
promoted tumorigenesis in the
;
model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research, Inc</pub><pmid>28416491</pmid><doi>10.1158/0008-5472.can-16-3472</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-3662-3846</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2017-05, Vol.77 (10), p.2620-2632 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5468752 |
| source | EZB Electronic Journals Library |
| subjects | Adenomatous Polyposis Coli Protein - deficiency Adhesins Age Animals Bacteria Bacteria - classification Bacteria - genetics Cancer Carcinogenesis Cell Transformation, Neoplastic Clinical isolates Colon Colon cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - etiology Colorectal Neoplasms - pathology Disease Models, Animal Etiology Fusobacterium nucleatum Gastrointestinal Microbiome Germfree Gnotobiotic Human health and pathology Hépatology and Gastroenterology Inflammation Inflammation - complications Inflammation - pathology Interleukin 1 Interleukin 10 Interleukin-10 - deficiency Large intestine Life Sciences Mice Mice, Knockout Mice, Transgenic Microbiomes Microbiota Small intestine Specific pathogen free Tumorigenesis Tumors |
| title | Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T03%3A05%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Locoregional%20Effects%20of%20Microbiota%20in%20a%20Preclinical%20Model%20of%20Colon%20Carcinogenesis&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=Tomkovich,%20Sarah&rft.date=2017-05-15&rft.volume=77&rft.issue=10&rft.spage=2620&rft.epage=2632&rft.pages=2620-2632&rft.issn=0008-5472&rft.eissn=1538-7445&rft_id=info:doi/10.1158/0008-5472.can-16-3472&rft_dat=%3Cproquest_pubme%3E1889386826%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c676t-169422e4fa34f806e7667be0eaca53707e5ad2d777caf5aae5d986e195b83aca3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1983259211&rft_id=info:pmid/28416491&rfr_iscdi=true |