Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer
Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal f...
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| Veröffentlicht in: | Cancer letters 2013-07, Vol.335 (1), p.128-135 |
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| container_title | Cancer letters |
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| creator | Wu, Xiongyan Chen, Xuehua Zhou, Quan Li, Pu Yu, Beiqin Li, Jianfang Qu, Ying Yan, Jun Yu, Yingyan Yan, Min Zhu, Zhenggang Liu, Bingya Su, Liping |
| description | Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. Taken together, these results suggest that HGF may play a pivotal role in the regulatory circuit between gastric cancer cells and stromal fibroblasts, and neutralization of HGF inhibits both activation and tumor-promoting properties of CAFs. |
| doi_str_mv | 10.1016/j.canlet.2013.02.002 |
| format | Article |
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However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. Taken together, these results suggest that HGF may play a pivotal role in the regulatory circuit between gastric cancer cells and stromal fibroblasts, and neutralization of HGF inhibits both activation and tumor-promoting properties of CAFs.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2013.02.002</identifier><identifier>PMID: 23402812</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; Cancer-associated fibroblasts ; carcinogenesis ; Cell growth ; Cell Line, Tumor ; Cell Movement ; Cell Transformation, Neoplastic - metabolism ; Chemokine CXCL12 - metabolism ; Chemokines ; coculture ; Coculture Techniques ; Fibroblasts ; Gastric cancer ; Gene Expression ; Gene Knockdown Techniques ; Hematology, Oncology and Palliative Medicine ; hepatocyte growth factor ; Hepatocyte Growth Factor - genetics ; Hepatocyte Growth Factor - metabolism ; Hepatocyte Growth Factor - physiology ; HGF ; Humans ; Kinases ; Male ; Medical research ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; neutralization ; neutralizing antibodies ; Proteins ; RNA, Small Interfering - genetics ; Signal Transduction ; stomach neoplasms ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; stromal cells ; Tumor Burden ; Tumor Microenvironment ; Tumorigenesis</subject><ispartof>Cancer letters, 2013-07, Vol.335 (1), p.128-135</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. 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However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. Taken together, these results suggest that HGF may play a pivotal role in the regulatory circuit between gastric cancer cells and stromal fibroblasts, and neutralization of HGF inhibits both activation and tumor-promoting properties of CAFs.</description><subject>Animals</subject><subject>Cancer-associated fibroblasts</subject><subject>carcinogenesis</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Chemokines</subject><subject>coculture</subject><subject>Coculture Techniques</subject><subject>Fibroblasts</subject><subject>Gastric cancer</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>hepatocyte growth factor</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>Hepatocyte Growth Factor - physiology</subject><subject>HGF</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>neutralization</subject><subject>neutralizing antibodies</subject><subject>Proteins</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction</subject><subject>stomach neoplasms</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>stromal cells</subject><subject>Tumor Burden</subject><subject>Tumor Microenvironment</subject><subject>Tumorigenesis</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxS0EosvCN0AQiQuXhPG_JL0gVRVQpEocSs-W44yDlyRebKdovz0OKSD1wsWW7d97Gs8bQl5SqCjQ-t2hMnoeMVUMKK-AVQDsEdnRtmFlc97CY7IDDqLkLZdn5FmMBwCQopFPyRnjAlhL2Y4MV3jUyZtTwmII_mf6Vlhtkg9FXt2dThiLtEz5HFPwkx4L67rgu1HHlF98ccy3Pot_Q27AGaOLhZuLIRPBmSJXaTA8J0-sHiO-uN_35Pbjh6-XV-X1l0-fLy-uSyO5TKUwNZMSWsuthLoWuhGt6ClyJgGplrTre95IZvu-A8FF22gt2HmtLUjGLfA9ebv55rp-LBiTmlw0OI56Rr9ERbmsedvK3LM9efMAPfglzLk6RWuxEg2VmRIbZYKPMaBVx-AmHU6KglqDUAe1BaHWIBQwlYPIslf35ks3Yf9X9KfzGXi9AVZ7pYfgorq9yQ4yp8S5aOpMvN8IzP26cxhUNA5zM3sX0CTVe_e_Gh4amNHNzujxO54w_vutilmgbtZxWaeFcgBKueC_AHxRuWw</recordid><startdate>20130710</startdate><enddate>20130710</enddate><creator>Wu, Xiongyan</creator><creator>Chen, Xuehua</creator><creator>Zhou, Quan</creator><creator>Li, Pu</creator><creator>Yu, Beiqin</creator><creator>Li, Jianfang</creator><creator>Qu, Ying</creator><creator>Yan, Jun</creator><creator>Yu, Yingyan</creator><creator>Yan, Min</creator><creator>Zhu, Zhenggang</creator><creator>Liu, Bingya</creator><creator>Su, Liping</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>FBQ</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20130710</creationdate><title>Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer</title><author>Wu, Xiongyan ; Chen, Xuehua ; Zhou, Quan ; Li, Pu ; Yu, Beiqin ; Li, Jianfang ; Qu, Ying ; Yan, Jun ; Yu, Yingyan ; Yan, Min ; Zhu, Zhenggang ; Liu, Bingya ; Su, Liping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-4c625508f3f50664a7484d1e3250e1a51bdd3752fddb043487aa4296af0523f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Cancer-associated fibroblasts</topic><topic>carcinogenesis</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Chemokines</topic><topic>coculture</topic><topic>Coculture Techniques</topic><topic>Fibroblasts</topic><topic>Gastric cancer</topic><topic>Gene Expression</topic><topic>Gene Knockdown Techniques</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>hepatocyte growth factor</topic><topic>Hepatocyte Growth Factor - genetics</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>Hepatocyte Growth Factor - physiology</topic><topic>HGF</topic><topic>Humans</topic><topic>Kinases</topic><topic>Male</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>neutralization</topic><topic>neutralizing antibodies</topic><topic>Proteins</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction</topic><topic>stomach neoplasms</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><topic>stromal cells</topic><topic>Tumor Burden</topic><topic>Tumor Microenvironment</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Xiongyan</creatorcontrib><creatorcontrib>Chen, Xuehua</creatorcontrib><creatorcontrib>Zhou, Quan</creatorcontrib><creatorcontrib>Li, Pu</creatorcontrib><creatorcontrib>Yu, Beiqin</creatorcontrib><creatorcontrib>Li, Jianfang</creatorcontrib><creatorcontrib>Qu, Ying</creatorcontrib><creatorcontrib>Yan, Jun</creatorcontrib><creatorcontrib>Yu, Yingyan</creatorcontrib><creatorcontrib>Yan, Min</creatorcontrib><creatorcontrib>Zhu, Zhenggang</creatorcontrib><creatorcontrib>Liu, Bingya</creatorcontrib><creatorcontrib>Su, Liping</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Xiongyan</au><au>Chen, Xuehua</au><au>Zhou, Quan</au><au>Li, Pu</au><au>Yu, Beiqin</au><au>Li, Jianfang</au><au>Qu, Ying</au><au>Yan, Jun</au><au>Yu, Yingyan</au><au>Yan, Min</au><au>Zhu, Zhenggang</au><au>Liu, Bingya</au><au>Su, Liping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2013-07-10</date><risdate>2013</risdate><volume>335</volume><issue>1</issue><spage>128</spage><epage>135</epage><pages>128-135</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the mechanisms underlying stromal fibroblast activation and their promotion of tumor growth remain largely unknown in gastric cancer. Here, we show that normal fibroblasts (NFs) from non-cancerous regions of gastric cancer exhibit the traits of CAFs when grown together with gastric cancer cells in vivo. Activation of NFs can be induced by co-culture with gastric cancer cells, while deprivation of hepatocyte growth factor (HGF) using a neutralizing antibody inhibits the activation of NFs. Moreover, we identify HGF as an important factor from CAFs that acts in a paracrine manner to promote tumorigenesis in vitro and in vivo. 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| subjects | Animals Cancer-associated fibroblasts carcinogenesis Cell growth Cell Line, Tumor Cell Movement Cell Transformation, Neoplastic - metabolism Chemokine CXCL12 - metabolism Chemokines coculture Coculture Techniques Fibroblasts Gastric cancer Gene Expression Gene Knockdown Techniques Hematology, Oncology and Palliative Medicine hepatocyte growth factor Hepatocyte Growth Factor - genetics Hepatocyte Growth Factor - metabolism Hepatocyte Growth Factor - physiology HGF Humans Kinases Male Medical research Metastasis Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation neutralization neutralizing antibodies Proteins RNA, Small Interfering - genetics Signal Transduction stomach neoplasms Stomach Neoplasms - metabolism Stomach Neoplasms - pathology stromal cells Tumor Burden Tumor Microenvironment Tumorigenesis |
| title | Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer |
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