CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-β-induced breast cancer progression
[Display omitted] •TGF-β conditionally regulates CCL2 and CCL5 expression in breast cancer.•CCL2 induces macrophages and/or monocytes for elevated CCL22 secretion.•CCL22 favors Th2-cell accumulation within tumor microenvironment.•HighCCL2-LowCCL5 shifts Th1-Th2 balance towards Th2 cells during cance...
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| Veröffentlicht in: | Immunobiology (1979) 2018-02, Vol.223 (2), p.151-161 |
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| creator | Mandal, Palash Kumar Biswas, Subir Mandal, Gunjan Purohit, Suman Gupta, Arnab Majumdar (Giri), Amita Roy Chowdhury, Sougata Bhattacharyya, Arindam |
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•TGF-β conditionally regulates CCL2 and CCL5 expression in breast cancer.•CCL2 induces macrophages and/or monocytes for elevated CCL22 secretion.•CCL22 favors Th2-cell accumulation within tumor microenvironment.•HighCCL2-LowCCL5 shifts Th1-Th2 balance towards Th2 cells during cancer progression.
We investigated expressions of −CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-β (TGF-β) expression. We observed an inverse correlation of TGF-β expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-β expression. TGF-β stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7. Interestingly, a significant swing of Th1-Th2 ratio towards Th2 is seen within the primary tumors expressing moderate/high-CCL2-low/negative-CCL5. We observed that CCL2-CCR2 interaction induces monocytes/macrophages to secrete Th2-attracting chemokine CCL22 in vitro. Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion. Study in 4T1-BALB/c BCa mouse model demonstrated significant (p |
| doi_str_mv | 10.1016/j.imbio.2017.10.031 |
| format | Article |
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•TGF-β conditionally regulates CCL2 and CCL5 expression in breast cancer.•CCL2 induces macrophages and/or monocytes for elevated CCL22 secretion.•CCL22 favors Th2-cell accumulation within tumor microenvironment.•HighCCL2-LowCCL5 shifts Th1-Th2 balance towards Th2 cells during cancer progression.
We investigated expressions of −CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-β (TGF-β) expression. We observed an inverse correlation of TGF-β expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-β expression. TGF-β stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7. Interestingly, a significant swing of Th1-Th2 ratio towards Th2 is seen within the primary tumors expressing moderate/high-CCL2-low/negative-CCL5. We observed that CCL2-CCR2 interaction induces monocytes/macrophages to secrete Th2-attracting chemokine CCL22 in vitro. Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion. Study in 4T1-BALB/c BCa mouse model demonstrated significant (p<0.05) decrease in CCL2, CCL5 and CCL22 levels and reduction in lung metastatic nodule numbers upon administering TGF-β inhibitor. These findings collectively indicate that TGF-β regulates CCL2 and CCL5 expression in a stage-dependent manner during BCa progression, which in turn, determines Th1-Th2 balance within the tumor microenvironment.</description><identifier>ISSN: 0171-2985</identifier><identifier>EISSN: 1878-3279</identifier><identifier>DOI: 10.1016/j.imbio.2017.10.031</identifier><identifier>PMID: 29107385</identifier><language>eng</language><publisher>Netherlands: Elsevier GmbH</publisher><subject>Animals ; Breast cancer ; Breast Neoplasms - immunology ; Breast Neoplasms - pathology ; Carcinogenesis ; CCL2 ; CCL22 ; CCL5 ; Chemokine CCL2 - genetics ; Chemokine CCL2 - metabolism ; Chemokine CCL22 - metabolism ; Chemokine CCL5 - genetics ; Chemokine CCL5 - metabolism ; Disease Models, Animal ; Disease Progression ; Female ; Humans ; Lung Neoplasms - immunology ; Lung Neoplasms - secondary ; Macrophages - immunology ; MCF-7 Cells ; Mice ; Mice, Inbred BALB C ; TGF-β ; Th1-Th2 Balance ; Th1-Th2 ratio ; Th2 Cells - immunology ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism</subject><ispartof>Immunobiology (1979), 2018-02, Vol.223 (2), p.151-161</ispartof><rights>2017 Elsevier GmbH</rights><rights>Copyright © 2017 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-981a32678a8b78d9643ce8c893573b8b8478d9f73ec933893f4f66758cca20a13</citedby><cites>FETCH-LOGICAL-c359t-981a32678a8b78d9643ce8c893573b8b8478d9f73ec933893f4f66758cca20a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.imbio.2017.10.031$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29107385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mandal, Palash Kumar</creatorcontrib><creatorcontrib>Biswas, Subir</creatorcontrib><creatorcontrib>Mandal, Gunjan</creatorcontrib><creatorcontrib>Purohit, Suman</creatorcontrib><creatorcontrib>Gupta, Arnab</creatorcontrib><creatorcontrib>Majumdar (Giri), Amita</creatorcontrib><creatorcontrib>Roy Chowdhury, Sougata</creatorcontrib><creatorcontrib>Bhattacharyya, Arindam</creatorcontrib><title>CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-β-induced breast cancer progression</title><title>Immunobiology (1979)</title><addtitle>Immunobiology</addtitle><description>[Display omitted]
•TGF-β conditionally regulates CCL2 and CCL5 expression in breast cancer.•CCL2 induces macrophages and/or monocytes for elevated CCL22 secretion.•CCL22 favors Th2-cell accumulation within tumor microenvironment.•HighCCL2-LowCCL5 shifts Th1-Th2 balance towards Th2 cells during cancer progression.
We investigated expressions of −CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-β (TGF-β) expression. We observed an inverse correlation of TGF-β expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-β expression. TGF-β stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7. Interestingly, a significant swing of Th1-Th2 ratio towards Th2 is seen within the primary tumors expressing moderate/high-CCL2-low/negative-CCL5. We observed that CCL2-CCR2 interaction induces monocytes/macrophages to secrete Th2-attracting chemokine CCL22 in vitro. Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion. Study in 4T1-BALB/c BCa mouse model demonstrated significant (p<0.05) decrease in CCL2, CCL5 and CCL22 levels and reduction in lung metastatic nodule numbers upon administering TGF-β inhibitor. These findings collectively indicate that TGF-β regulates CCL2 and CCL5 expression in a stage-dependent manner during BCa progression, which in turn, determines Th1-Th2 balance within the tumor microenvironment.</description><subject>Animals</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinogenesis</subject><subject>CCL2</subject><subject>CCL22</subject><subject>CCL5</subject><subject>Chemokine CCL2 - genetics</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Chemokine CCL22 - metabolism</subject><subject>Chemokine CCL5 - genetics</subject><subject>Chemokine CCL5 - metabolism</subject><subject>Disease Models, Animal</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - secondary</subject><subject>Macrophages - immunology</subject><subject>MCF-7 Cells</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>TGF-β</subject><subject>Th1-Th2 Balance</subject><subject>Th1-Th2 ratio</subject><subject>Th2 Cells - immunology</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>0171-2985</issn><issn>1878-3279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1qGzEURkVIaJykT1AoWmYjVz-ekbToopjECRiycdZCI91xZGY0rjRTyGv1QfpM0cRpl10JvnuuPu5B6AujS0ZZ_e2wDH0ThiWnTJZkSQU7QwumpCKCS32OFmXACNequkRXOR8oZZpL9Qldcs2oFKpaoLhebzl2Q_RhDEO0XfeKPYyQ-hAh43nKiYcjRA9xxLsXTqxzUz91duaxn1KIe7zb3JM_v0mIfnLgcZPA5hE7Gx0kfEzDPkHOhb9BF63tMnz-eK_R8_3dbv1Atk-bx_WPLXGi0iPRilnBa6msaqTyul4JB8opLSopGtWo1Zy2UoDTQpS4XbV1LSvlnOXUMnGNbk__lu6fE-TR9CE76DobYZiyYbpmtdC1kAUVJ9SlIecErTmm0Nv0ahg1s2hzMO-izSx6DovosvX1o2BqevD_dv6aLcD3EwDlzF8BkskuQPHhQwI3Gj-E_xa8AUlrkDs</recordid><startdate>201802</startdate><enddate>201802</enddate><creator>Mandal, Palash Kumar</creator><creator>Biswas, Subir</creator><creator>Mandal, Gunjan</creator><creator>Purohit, Suman</creator><creator>Gupta, Arnab</creator><creator>Majumdar (Giri), Amita</creator><creator>Roy Chowdhury, Sougata</creator><creator>Bhattacharyya, Arindam</creator><general>Elsevier GmbH</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>201802</creationdate><title>CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-β-induced breast cancer progression</title><author>Mandal, Palash Kumar ; Biswas, Subir ; Mandal, Gunjan ; Purohit, Suman ; Gupta, Arnab ; Majumdar (Giri), Amita ; Roy Chowdhury, Sougata ; Bhattacharyya, Arindam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-981a32678a8b78d9643ce8c893573b8b8478d9f73ec933893f4f66758cca20a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinogenesis</topic><topic>CCL2</topic><topic>CCL22</topic><topic>CCL5</topic><topic>Chemokine CCL2 - genetics</topic><topic>Chemokine CCL2 - metabolism</topic><topic>Chemokine CCL22 - metabolism</topic><topic>Chemokine CCL5 - genetics</topic><topic>Chemokine CCL5 - metabolism</topic><topic>Disease Models, Animal</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - secondary</topic><topic>Macrophages - immunology</topic><topic>MCF-7 Cells</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>TGF-β</topic><topic>Th1-Th2 Balance</topic><topic>Th1-Th2 ratio</topic><topic>Th2 Cells - immunology</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mandal, Palash Kumar</creatorcontrib><creatorcontrib>Biswas, Subir</creatorcontrib><creatorcontrib>Mandal, Gunjan</creatorcontrib><creatorcontrib>Purohit, Suman</creatorcontrib><creatorcontrib>Gupta, Arnab</creatorcontrib><creatorcontrib>Majumdar (Giri), Amita</creatorcontrib><creatorcontrib>Roy Chowdhury, Sougata</creatorcontrib><creatorcontrib>Bhattacharyya, Arindam</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>Immunobiology (1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mandal, Palash Kumar</au><au>Biswas, Subir</au><au>Mandal, Gunjan</au><au>Purohit, Suman</au><au>Gupta, Arnab</au><au>Majumdar (Giri), Amita</au><au>Roy Chowdhury, Sougata</au><au>Bhattacharyya, Arindam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-β-induced breast cancer progression</atitle><jtitle>Immunobiology (1979)</jtitle><addtitle>Immunobiology</addtitle><date>2018-02</date><risdate>2018</risdate><volume>223</volume><issue>2</issue><spage>151</spage><epage>161</epage><pages>151-161</pages><issn>0171-2985</issn><eissn>1878-3279</eissn><abstract>[Display omitted]
•TGF-β conditionally regulates CCL2 and CCL5 expression in breast cancer.•CCL2 induces macrophages and/or monocytes for elevated CCL22 secretion.•CCL22 favors Th2-cell accumulation within tumor microenvironment.•HighCCL2-LowCCL5 shifts Th1-Th2 balance towards Th2 cells during cancer progression.
We investigated expressions of −CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-β (TGF-β) expression. We observed an inverse correlation of TGF-β expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-β expression. TGF-β stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7. Interestingly, a significant swing of Th1-Th2 ratio towards Th2 is seen within the primary tumors expressing moderate/high-CCL2-low/negative-CCL5. We observed that CCL2-CCR2 interaction induces monocytes/macrophages to secrete Th2-attracting chemokine CCL22 in vitro. Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion. Study in 4T1-BALB/c BCa mouse model demonstrated significant (p<0.05) decrease in CCL2, CCL5 and CCL22 levels and reduction in lung metastatic nodule numbers upon administering TGF-β inhibitor. These findings collectively indicate that TGF-β regulates CCL2 and CCL5 expression in a stage-dependent manner during BCa progression, which in turn, determines Th1-Th2 balance within the tumor microenvironment.</abstract><cop>Netherlands</cop><pub>Elsevier GmbH</pub><pmid>29107385</pmid><doi>10.1016/j.imbio.2017.10.031</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Breast cancer Breast Neoplasms - immunology Breast Neoplasms - pathology Carcinogenesis CCL2 CCL22 CCL5 Chemokine CCL2 - genetics Chemokine CCL2 - metabolism Chemokine CCL22 - metabolism Chemokine CCL5 - genetics Chemokine CCL5 - metabolism Disease Models, Animal Disease Progression Female Humans Lung Neoplasms - immunology Lung Neoplasms - secondary Macrophages - immunology MCF-7 Cells Mice Mice, Inbred BALB C TGF-β Th1-Th2 Balance Th1-Th2 ratio Th2 Cells - immunology Transforming Growth Factor beta - genetics Transforming Growth Factor beta - metabolism |
| title | CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-β-induced breast cancer progression |
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