Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches

•Fibroblasts play an essential role in gastric cancer peritoneal metastasis.•CXCR7+ fibroblasts significantly enriched in peritoneal metastases.•CLDN11 secreted by CXCR7+ fibroblasts promotes gastric cancer peritoneal metastasis. Fibroblasts are necessary to the progression of cancer. However, the r...

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Veröffentlicht in:International immunopharmacology 2024-03, Vol.129, p.111647-111647, Article 111647
Hauptverfasser: Liu, Kanghui, Wang, Yanjuan, Shao, Wenwen, Tang, Chong, Zhao, Siguo, Xu, Jiafeng, Xu, Peng, Cheng, Quan, Huang, Shansong, Ji, Peicheng, Qiu, Shengkui
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container_issue
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container_title International immunopharmacology
container_volume 129
creator Liu, Kanghui
Wang, Yanjuan
Shao, Wenwen
Tang, Chong
Zhao, Siguo
Xu, Jiafeng
Xu, Peng
Cheng, Quan
Huang, Shansong
Ji, Peicheng
Qiu, Shengkui
description •Fibroblasts play an essential role in gastric cancer peritoneal metastasis.•CXCR7+ fibroblasts significantly enriched in peritoneal metastases.•CLDN11 secreted by CXCR7+ fibroblasts promotes gastric cancer peritoneal metastasis. Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.
doi_str_mv 10.1016/j.intimp.2024.111647
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Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2024.111647</identifier><identifier>PMID: 38335659</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Cell Line, Tumor ; Cell Proliferation ; Claudins ; CLDN11 ; CXCR7 ; Fibroblasts ; Fibroblasts - metabolism ; Gastric cancer peritoneal metastasis ; Humans ; Peritoneal Neoplasms - genetics ; Signal Transduction ; Single cell sequencing ; Stomach Neoplasms - pathology ; Tumor Microenvironment</subject><ispartof>International immunopharmacology, 2024-03, Vol.129, p.111647-111647, Article 111647</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-f000c797529f172dc2143b0a5664ec9412f506a618ec91dc946ac91db81529493</citedby><cites>FETCH-LOGICAL-c362t-f000c797529f172dc2143b0a5664ec9412f506a618ec91dc946ac91db81529493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2024.111647$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38335659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Kanghui</creatorcontrib><creatorcontrib>Wang, Yanjuan</creatorcontrib><creatorcontrib>Shao, Wenwen</creatorcontrib><creatorcontrib>Tang, Chong</creatorcontrib><creatorcontrib>Zhao, Siguo</creatorcontrib><creatorcontrib>Xu, Jiafeng</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Cheng, Quan</creatorcontrib><creatorcontrib>Huang, Shansong</creatorcontrib><creatorcontrib>Ji, Peicheng</creatorcontrib><creatorcontrib>Qiu, Shengkui</creatorcontrib><title>Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•Fibroblasts play an essential role in gastric cancer peritoneal metastasis.•CXCR7+ fibroblasts significantly enriched in peritoneal metastases.•CLDN11 secreted by CXCR7+ fibroblasts promotes gastric cancer peritoneal metastasis. Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.</description><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Claudins</subject><subject>CLDN11</subject><subject>CXCR7</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Gastric cancer peritoneal metastasis</subject><subject>Humans</subject><subject>Peritoneal Neoplasms - genetics</subject><subject>Signal Transduction</subject><subject>Single cell sequencing</subject><subject>Stomach Neoplasms - pathology</subject><subject>Tumor Microenvironment</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uc1u1DAQjhCIlsIbIOQjlyweJ3aSCxJaflppBRd6thxnsutVYgfbW8HT8KpMlMKRk2fG38_YX1G8Br4DDurdeed8dvOyE1zUOwBQdfOkuIa2aUtouHxKtVRNKRvVXRUvUjpzTvManhdXVVtVUsnuuvh97x_QTc4fWT4hC96GI3pnWQwTtSPbHz5-BSgT2oh5hY2uj6GfTMqJOc-OVETCW-MtRrZgdDl4NBObMdOdSS6RdAyX44klEpiwtDhNLOGPC3q7Sho_MPy5Umf0mahmWWIw9oTpZfFsNFPCV4_nTXH_-dP3_W15-Pblbv_hUNpKiVyOnHPbdI0U3QiNGKyAuuq5kUrVaLsaxCi5Mgpa6mCgiTJr0bdAlLqrboq3my4Z014p69mldU_jMVySFp2QvOrIjKD1BrUxpBRx1AstbuIvDVyv0eiz3qLRazR6i4Zobx4dLv2Mwz_S3ywI8H4DIL3zwWHUyTr6IRxcRJv1ENz_Hf4A2kSkkQ</recordid><startdate>20240310</startdate><enddate>20240310</enddate><creator>Liu, Kanghui</creator><creator>Wang, Yanjuan</creator><creator>Shao, Wenwen</creator><creator>Tang, Chong</creator><creator>Zhao, Siguo</creator><creator>Xu, Jiafeng</creator><creator>Xu, Peng</creator><creator>Cheng, Quan</creator><creator>Huang, Shansong</creator><creator>Ji, Peicheng</creator><creator>Qiu, Shengkui</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20240310</creationdate><title>Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches</title><author>Liu, Kanghui ; Wang, Yanjuan ; Shao, Wenwen ; Tang, Chong ; Zhao, Siguo ; Xu, Jiafeng ; Xu, Peng ; Cheng, Quan ; Huang, Shansong ; Ji, Peicheng ; Qiu, Shengkui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-f000c797529f172dc2143b0a5664ec9412f506a618ec91dc946ac91db81529493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Claudins</topic><topic>CLDN11</topic><topic>CXCR7</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Gastric cancer peritoneal metastasis</topic><topic>Humans</topic><topic>Peritoneal Neoplasms - genetics</topic><topic>Signal Transduction</topic><topic>Single cell sequencing</topic><topic>Stomach Neoplasms - pathology</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Kanghui</creatorcontrib><creatorcontrib>Wang, Yanjuan</creatorcontrib><creatorcontrib>Shao, Wenwen</creatorcontrib><creatorcontrib>Tang, Chong</creatorcontrib><creatorcontrib>Zhao, Siguo</creatorcontrib><creatorcontrib>Xu, Jiafeng</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Cheng, Quan</creatorcontrib><creatorcontrib>Huang, Shansong</creatorcontrib><creatorcontrib>Ji, Peicheng</creatorcontrib><creatorcontrib>Qiu, Shengkui</creatorcontrib><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><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Kanghui</au><au>Wang, Yanjuan</au><au>Shao, Wenwen</au><au>Tang, Chong</au><au>Zhao, Siguo</au><au>Xu, Jiafeng</au><au>Xu, Peng</au><au>Cheng, Quan</au><au>Huang, Shansong</au><au>Ji, Peicheng</au><au>Qiu, Shengkui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2024-03-10</date><risdate>2024</risdate><volume>129</volume><spage>111647</spage><epage>111647</epage><pages>111647-111647</pages><artnum>111647</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•Fibroblasts play an essential role in gastric cancer peritoneal metastasis.•CXCR7+ fibroblasts significantly enriched in peritoneal metastases.•CLDN11 secreted by CXCR7+ fibroblasts promotes gastric cancer peritoneal metastasis. Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38335659</pmid><doi>10.1016/j.intimp.2024.111647</doi><tpages>1</tpages></addata></record>
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subjects Cell Line, Tumor
Cell Proliferation
Claudins
CLDN11
CXCR7
Fibroblasts
Fibroblasts - metabolism
Gastric cancer peritoneal metastasis
Humans
Peritoneal Neoplasms - genetics
Signal Transduction
Single cell sequencing
Stomach Neoplasms - pathology
Tumor Microenvironment
title Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches
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