Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer
Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermor...
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| Veröffentlicht in: | Cancers 2023-01, Vol.15 (3), p.606 |
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| creator | Ueki, Akane Komura, Masayuki Koshino, Akira Wang, Chengbo Nagao, Kazuhiro Homochi, Mai Tsukada, Yuki Ebi, Masahide Ogasawara, Naotaka Tsuzuki, Toyonori Kasai, Kenji Kasugai, Kunio Takahashi, Satoru Inaguma, Shingo |
| description | Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%;
= 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (
= 0.0031) and distant organ metastasis (
< 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells. |
| doi_str_mv | 10.3390/cancers15030606 |
| format | Article |
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= 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (
= 0.0031) and distant organ metastasis (
< 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15030606</identifier><identifier>PMID: 36765564</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>AKT protein ; Cancer ; Cancer cells ; Cancer therapies ; Cell activation ; Cell culture ; Cell interactions ; Cell migration ; Cells ; Colorectal cancer ; Colorectal carcinoma ; Decorin ; Extracellular matrix ; Fibroblast activation protein ; Fibroblasts ; Gene expression ; Health aspects ; Hypothesis testing ; Medical prognosis ; Metastases ; Metastasis ; Motility ; Mutation ; p53 Protein ; Patients ; Peritoneum ; Phenotypes ; Prognosis ; Software ; Stat3 protein ; Stromal cells ; Tumors</subject><ispartof>Cancers, 2023-01, Vol.15 (3), p.606</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-68cc3ea6a2bdca81db6b075ccc0cfc230949d772e3e26248df2806bb05e6fe153</citedby><cites>FETCH-LOGICAL-c554t-68cc3ea6a2bdca81db6b075ccc0cfc230949d772e3e26248df2806bb05e6fe153</cites><orcidid>0000-0001-8848-5804 ; 0000-0002-0002-6548 ; 0000-0001-8585-8900 ; 0000-0002-7762-8512 ; 0000-0002-4855-4366 ; 0000-0002-8139-8158</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913098/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913098/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36765564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ueki, Akane</creatorcontrib><creatorcontrib>Komura, Masayuki</creatorcontrib><creatorcontrib>Koshino, Akira</creatorcontrib><creatorcontrib>Wang, Chengbo</creatorcontrib><creatorcontrib>Nagao, Kazuhiro</creatorcontrib><creatorcontrib>Homochi, Mai</creatorcontrib><creatorcontrib>Tsukada, Yuki</creatorcontrib><creatorcontrib>Ebi, Masahide</creatorcontrib><creatorcontrib>Ogasawara, Naotaka</creatorcontrib><creatorcontrib>Tsuzuki, Toyonori</creatorcontrib><creatorcontrib>Kasai, Kenji</creatorcontrib><creatorcontrib>Kasugai, Kunio</creatorcontrib><creatorcontrib>Takahashi, Satoru</creatorcontrib><creatorcontrib>Inaguma, Shingo</creatorcontrib><title>Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%;
= 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (
= 0.0031) and distant organ metastasis (
< 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.</description><subject>AKT protein</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cancer therapies</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell interactions</subject><subject>Cell migration</subject><subject>Cells</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Decorin</subject><subject>Extracellular matrix</subject><subject>Fibroblast activation protein</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>Hypothesis testing</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Motility</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Patients</subject><subject>Peritoneum</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Software</subject><subject>Stat3 protein</subject><subject>Stromal cells</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</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>eNptks1v3CAQxVHVqomSnHurkHrpZRMMBuxLpdRKk0pJs9KmZ4THOEtkwxbwSvnvizcfTaLCATT83hs9NAh9KsgxYzU5Ae3AhFhwwogg4h3ap0TShRB1-f7FfQ8dxXhH8mKskEJ-RHtMSMG5KPfRZpWCH_WAl9erm1_4zK1n04ivfLKDTffY9_i7T2vc7Jph7Tr8JGnMMMRdZRlMZyFFvPQ-4NUUtnabAetw4wcfDKQZ3zkcog-9HqI5ejwP0O8fZzfNxeLy-vxnc3q5AM7LtBAVADNaaNp2oKuia0VLJAcAAj1QRuqy7qSkhhkqaFl1Pa2IaFvCjehNwdkB-vbgu5na0XRgXAp6UJtgRx3ulddWvX5xdq1u_VbVdZHdq2zw9dEg-D-TiUmNNkKOrJ3xU1RUSi4orxjN6Jc36J2fgsvxZqqsKsFK_o-61YNR1vU-94XZVJ3KkpHclMtMHf-HyrszowXvTG9z_ZXg5EEAwccYTP-csSBqnhP1Zk6y4vPLr3nmn6aC_QXVH7mS</recordid><startdate>20230118</startdate><enddate>20230118</enddate><creator>Ueki, Akane</creator><creator>Komura, Masayuki</creator><creator>Koshino, Akira</creator><creator>Wang, Chengbo</creator><creator>Nagao, Kazuhiro</creator><creator>Homochi, Mai</creator><creator>Tsukada, Yuki</creator><creator>Ebi, Masahide</creator><creator>Ogasawara, Naotaka</creator><creator>Tsuzuki, Toyonori</creator><creator>Kasai, Kenji</creator><creator>Kasugai, Kunio</creator><creator>Takahashi, Satoru</creator><creator>Inaguma, Shingo</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8848-5804</orcidid><orcidid>https://orcid.org/0000-0002-0002-6548</orcidid><orcidid>https://orcid.org/0000-0001-8585-8900</orcidid><orcidid>https://orcid.org/0000-0002-7762-8512</orcidid><orcidid>https://orcid.org/0000-0002-4855-4366</orcidid><orcidid>https://orcid.org/0000-0002-8139-8158</orcidid></search><sort><creationdate>20230118</creationdate><title>Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer</title><author>Ueki, Akane ; 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To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%;
= 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (
= 0.0031) and distant organ metastasis (
< 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36765564</pmid><doi>10.3390/cancers15030606</doi><orcidid>https://orcid.org/0000-0001-8848-5804</orcidid><orcidid>https://orcid.org/0000-0002-0002-6548</orcidid><orcidid>https://orcid.org/0000-0001-8585-8900</orcidid><orcidid>https://orcid.org/0000-0002-7762-8512</orcidid><orcidid>https://orcid.org/0000-0002-4855-4366</orcidid><orcidid>https://orcid.org/0000-0002-8139-8158</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | AKT protein Cancer Cancer cells Cancer therapies Cell activation Cell culture Cell interactions Cell migration Cells Colorectal cancer Colorectal carcinoma Decorin Extracellular matrix Fibroblast activation protein Fibroblasts Gene expression Health aspects Hypothesis testing Medical prognosis Metastases Metastasis Motility Mutation p53 Protein Patients Peritoneum Phenotypes Prognosis Software Stat3 protein Stromal cells Tumors |
| title | Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer |
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