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Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer epithelial cells and fibroblasts
In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about t...
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| Published in: | PloS one 2012-03, Vol.7 (3), p.e33289-e33289 |
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| creator | Apostolopoulou, Maria Ligon, Lee |
| description | In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis. |
| doi_str_mv | 10.1371/journal.pone.0033289 |
| format | article |
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Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0033289</identifier><identifier>PMID: 22413011</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adhesion ; Antibodies ; Biology ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cadherins ; Cadherins - genetics ; Cadherins - metabolism ; Cancer ; Cancer metastasis ; Cell adhesion ; Cell adhesion & migration ; Cell Adhesion - genetics ; Cell culture ; Cell growth ; Cell Line ; Epithelial cells ; Epithelial Cells - metabolism ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoblotting ; Immunocytochemistry ; Interdisciplinary aspects ; Kinases ; Medicine ; Melanoma ; Metastases ; Metastasis ; Paracrine signalling ; Protein Transport ; Proteins ; RNA-mediated interference ; Stroma ; Tumor cells</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e33289-e33289</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Apostolopoulou, Ligon. 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Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Apostolopoulou, Maria</au><au>Ligon, Lee</au><au>Derksen, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer epithelial cells and fibroblasts</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-03-07</date><risdate>2012</risdate><volume>7</volume><issue>3</issue><spage>e33289</spage><epage>e33289</epage><pages>e33289-e33289</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22413011</pmid><doi>10.1371/journal.pone.0033289</doi><tpages>e33289</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adhesion Antibodies Biology Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Cadherins Cadherins - genetics Cadherins - metabolism Cancer Cancer metastasis Cell adhesion Cell adhesion & migration Cell Adhesion - genetics Cell culture Cell growth Cell Line Epithelial cells Epithelial Cells - metabolism Female Fibroblasts Fibroblasts - metabolism Gene Expression Gene Expression Regulation, Neoplastic Humans Immunoblotting Immunocytochemistry Interdisciplinary aspects Kinases Medicine Melanoma Metastases Metastasis Paracrine signalling Protein Transport Proteins RNA-mediated interference Stroma Tumor cells |
| title | Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer epithelial cells and fibroblasts |
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