Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer
Background Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive. Methods To investigate the underlying mechanism involved in the regulation of...
Gespeichert in:
| Veröffentlicht in: | Journal of cancer research and clinical oncology 2023-07, Vol.149 (8), p.4477-4487 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4487 |
|---|---|
| container_issue | 8 |
| container_start_page | 4477 |
| container_title | Journal of cancer research and clinical oncology |
| container_volume | 149 |
| creator | Park, Seo-Gyu Ji, Mi-Jung Ham, In-Hye Shin, Yoon-Hee Lee, Su-Min Lee, Chang Hoon Kim, Eunjung Hur, Hoon Park, Hyun-Mee Kim, Jae-Young |
| description | Background
Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.
Methods
To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC–MS/MS.
Results
We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.
Conclusions
The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC. |
| doi_str_mv | 10.1007/s00432-022-04361-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2716090197</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2716090197</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-2f7e97c946472930ac41cf9d42513beece776b93db2a7d02ab4b87683b274f913</originalsourceid><addsrcrecordid>eNp9kc1O3DAURq2KqkyhL9AFssSGTYp_48kSjVqoNBILytqynZvBKImntlPIa_DEeBgKUhddWFe2zz3X8ofQV0q-UULUeSJEcFYRVpbgNa3mD2hBd0eUc3mAFoQqWklG60P0OaV7UvZSsU_osMBMSi4X6OkGXIQcBsBmNP2cfMIR_oDpd7WdHLQYHrcRUvJhxKHDq-u1uGDYj_hu3oZH77Azo4NYmZSC8yaXjs7bGGxvUk74wec7bHCehhCrbQxDyH7c4G4aXd4pi2hTwPgmOkYfuzIevrzWI3T74_uv1VW1vr78ubpYV44rmSvWKWiUa0QtFGs4MU5Q1zWtYJJyC-BAqdo2vLXMqJYwY4VdqnrJLVOiayg_Qmd7b3nU7wlS1oNPDvrejBCmpJmiNWkIbVRBT_9B78MUy38VaslVzeSSyEKxPeViSClCp7fRDybOmhK9S0zvE9MlMf2SmJ5L08mrerIDtG8tfyMqAN8DqVyNG4jvs_-jfQbCZ6Ou</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2837625805</pqid></control><display><type>article</type><title>Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer</title><source>SpringerLink Journals - AutoHoldings</source><creator>Park, Seo-Gyu ; Ji, Mi-Jung ; Ham, In-Hye ; Shin, Yoon-Hee ; Lee, Su-Min ; Lee, Chang Hoon ; Kim, Eunjung ; Hur, Hoon ; Park, Hyun-Mee ; Kim, Jae-Young</creator><creatorcontrib>Park, Seo-Gyu ; Ji, Mi-Jung ; Ham, In-Hye ; Shin, Yoon-Hee ; Lee, Su-Min ; Lee, Chang Hoon ; Kim, Eunjung ; Hur, Hoon ; Park, Hyun-Mee ; Kim, Jae-Young</creatorcontrib><description>Background
Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.
Methods
To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC–MS/MS.
Results
We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.
Conclusions
The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-022-04361-y</identifier><identifier>PMID: 36125535</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cancer Research ; Cell migration ; Fibroblasts ; Gastric cancer ; Hematology ; Hypoxia ; Hypoxia-inducible factor 1a ; Internal Medicine ; Mass spectroscopy ; Medicine ; Medicine & Public Health ; Oncology ; Secretome ; Trypsin ; Tumor microenvironment ; Tumors</subject><ispartof>Journal of cancer research and clinical oncology, 2023-07, Vol.149 (8), p.4477-4487</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-2f7e97c946472930ac41cf9d42513beece776b93db2a7d02ab4b87683b274f913</citedby><cites>FETCH-LOGICAL-c375t-2f7e97c946472930ac41cf9d42513beece776b93db2a7d02ab4b87683b274f913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-022-04361-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-022-04361-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36125535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Seo-Gyu</creatorcontrib><creatorcontrib>Ji, Mi-Jung</creatorcontrib><creatorcontrib>Ham, In-Hye</creatorcontrib><creatorcontrib>Shin, Yoon-Hee</creatorcontrib><creatorcontrib>Lee, Su-Min</creatorcontrib><creatorcontrib>Lee, Chang Hoon</creatorcontrib><creatorcontrib>Kim, Eunjung</creatorcontrib><creatorcontrib>Hur, Hoon</creatorcontrib><creatorcontrib>Park, Hyun-Mee</creatorcontrib><creatorcontrib>Kim, Jae-Young</creatorcontrib><title>Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Background
Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.
Methods
To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC–MS/MS.
Results
We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.
Conclusions
The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.</description><subject>Cancer Research</subject><subject>Cell migration</subject><subject>Fibroblasts</subject><subject>Gastric cancer</subject><subject>Hematology</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factor 1a</subject><subject>Internal Medicine</subject><subject>Mass spectroscopy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Secretome</subject><subject>Trypsin</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1O3DAURq2KqkyhL9AFssSGTYp_48kSjVqoNBILytqynZvBKImntlPIa_DEeBgKUhddWFe2zz3X8ofQV0q-UULUeSJEcFYRVpbgNa3mD2hBd0eUc3mAFoQqWklG60P0OaV7UvZSsU_osMBMSi4X6OkGXIQcBsBmNP2cfMIR_oDpd7WdHLQYHrcRUvJhxKHDq-u1uGDYj_hu3oZH77Azo4NYmZSC8yaXjs7bGGxvUk74wec7bHCehhCrbQxDyH7c4G4aXd4pi2hTwPgmOkYfuzIevrzWI3T74_uv1VW1vr78ubpYV44rmSvWKWiUa0QtFGs4MU5Q1zWtYJJyC-BAqdo2vLXMqJYwY4VdqnrJLVOiayg_Qmd7b3nU7wlS1oNPDvrejBCmpJmiNWkIbVRBT_9B78MUy38VaslVzeSSyEKxPeViSClCp7fRDybOmhK9S0zvE9MlMf2SmJ5L08mrerIDtG8tfyMqAN8DqVyNG4jvs_-jfQbCZ6Ou</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Park, Seo-Gyu</creator><creator>Ji, Mi-Jung</creator><creator>Ham, In-Hye</creator><creator>Shin, Yoon-Hee</creator><creator>Lee, Su-Min</creator><creator>Lee, Chang Hoon</creator><creator>Kim, Eunjung</creator><creator>Hur, Hoon</creator><creator>Park, Hyun-Mee</creator><creator>Kim, Jae-Young</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20230701</creationdate><title>Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer</title><author>Park, Seo-Gyu ; Ji, Mi-Jung ; Ham, In-Hye ; Shin, Yoon-Hee ; Lee, Su-Min ; Lee, Chang Hoon ; Kim, Eunjung ; Hur, Hoon ; Park, Hyun-Mee ; Kim, Jae-Young</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-2f7e97c946472930ac41cf9d42513beece776b93db2a7d02ab4b87683b274f913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Cancer Research</topic><topic>Cell migration</topic><topic>Fibroblasts</topic><topic>Gastric cancer</topic><topic>Hematology</topic><topic>Hypoxia</topic><topic>Hypoxia-inducible factor 1a</topic><topic>Internal Medicine</topic><topic>Mass spectroscopy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Secretome</topic><topic>Trypsin</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Seo-Gyu</creatorcontrib><creatorcontrib>Ji, Mi-Jung</creatorcontrib><creatorcontrib>Ham, In-Hye</creatorcontrib><creatorcontrib>Shin, Yoon-Hee</creatorcontrib><creatorcontrib>Lee, Su-Min</creatorcontrib><creatorcontrib>Lee, Chang Hoon</creatorcontrib><creatorcontrib>Kim, Eunjung</creatorcontrib><creatorcontrib>Hur, Hoon</creatorcontrib><creatorcontrib>Park, Hyun-Mee</creatorcontrib><creatorcontrib>Kim, Jae-Young</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Seo-Gyu</au><au>Ji, Mi-Jung</au><au>Ham, In-Hye</au><au>Shin, Yoon-Hee</au><au>Lee, Su-Min</au><au>Lee, Chang Hoon</au><au>Kim, Eunjung</au><au>Hur, Hoon</au><au>Park, Hyun-Mee</au><au>Kim, Jae-Young</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>149</volume><issue>8</issue><spage>4477</spage><epage>4487</epage><pages>4477-4487</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Background
Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.
Methods
To investigate the underlying mechanism involved in the regulation of gastric cancer (GC) progression by hypoxic CAFs, we performed secretome profiling. Normoxic or hypoxic CAFs conditioned media (CM) were filter-concentrated and in-gel trypsin digested. Resulting peptides were analyzed with LC–MS/MS.
Results
We observed that CM derived from hypoxic CAFs could promote migration of a panel of GC cell lines (AGS, SNU668, SNU638). Mass spectrometry analysis of hypoxic or normoxic CAFs CM identified 1595 proteins, of which 19 proteins (10 upregulated and 9 downregulated) were differentially expressed in the hypoxic secretome. We focused on COL4A2, whose expression was significantly decreased in hypoxic CAFs in HIF-1α-independent manner. Silencing of COL4A2 expression in normoxic CAFs phenocopied the effect of hypoxic CAFs in promoting GC cell migration.
Conclusions
The reduced expression of COL4A2 in a hypoxic environment might be associated with the tumor-promoting role of hypoxic CAFs in GC.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36125535</pmid><doi>10.1007/s00432-022-04361-y</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0171-5216 |
| ispartof | Journal of cancer research and clinical oncology, 2023-07, Vol.149 (8), p.4477-4487 |
| issn | 0171-5216 1432-1335 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2716090197 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Cancer Research Cell migration Fibroblasts Gastric cancer Hematology Hypoxia Hypoxia-inducible factor 1a Internal Medicine Mass spectroscopy Medicine Medicine & Public Health Oncology Secretome Trypsin Tumor microenvironment Tumors |
| title | Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T14%3A30%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Secretome%20analysis%20reveals%20reduced%20expression%20of%20COL4A2%20in%20hypoxic%20cancer-associated%20fibroblasts%20with%20a%20tumor-promoting%20function%20in%20gastric%20cancer&rft.jtitle=Journal%20of%20cancer%20research%20and%20clinical%20oncology&rft.au=Park,%20Seo-Gyu&rft.date=2023-07-01&rft.volume=149&rft.issue=8&rft.spage=4477&rft.epage=4487&rft.pages=4477-4487&rft.issn=0171-5216&rft.eissn=1432-1335&rft_id=info:doi/10.1007/s00432-022-04361-y&rft_dat=%3Cproquest_cross%3E2716090197%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2837625805&rft_id=info:pmid/36125535&rfr_iscdi=true |