Heriberto Moran, Limary M Cancel, Mariya A Mayer, Henry Qazi, Lance L Munn, John M Tarbell
{"title":"癌细胞糖萼蛋白聚糖Glypican-1介导间质流动机械转导，促进细胞迁移和转移。","authors":"Heriberto Moran, Limary M Cancel, Mariya A Mayer, Henry Qazi, Lance L Munn, John M Tarbell","doi":"10.3233/BIR-180203","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that the glycosaminoglycans (GAGs) heparan sulfate (HS) and hyaluronic acid (HA) are mechanosensors for interstitial flow on cancer cells. The proteins that link the GAGs to the cancer cell for mechanotransduction, however, are not known.</p><p><strong>Objective: </strong>To assess whether the HS proteoglycan core proteins, Glypican-1 and Syndecan-1, or the HA receptor, CD44, provides the mechanical linkage to the cell.</p><p><strong>Methods: </strong>The highly metastatic renal carcinoma cell line (SN12L1) and its companion low metastatic cell line (SN12C) were analyzed by Western blot, siRNA, and a 3-dimensional interstitial flow migration assay.</p><p><strong>Results: </strong>There was significant elevation of Glypican-1 protein expression in the SN12L1 cells relative to the SN12C cells while there were no significant differences in Syndecan-1 or CD44. Knock down of Glypican-1 by siRNA completely blocked flow induced migration in SN12L1 cells. MAPK inhibitors also blocked flow induced migration in SN12L1 cells.</p><p><strong>Conclusions: </strong>Glypican-1 provides the mechanical linkage from HS (the flow sensor) to the SN12L1 cell where mechanotransduction leading to the enhancement of migration (metastasis) occurs. MAPKs downstream of Glypican-1 propagate the signal. The HS, Glypican-1, MAPK signaling axis suggests opportunities for pharmaceutical intervention.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":" ","pages":"151-161"},"PeriodicalIF":0.8000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-180203","citationCount":"13","resultStr":"{\"title\":\"The cancer cell glycocalyx proteoglycan Glypican-1 mediates interstitial flow mechanotransduction to enhance cell migration and metastasis.\",\"authors\":\"Heriberto Moran, Limary M Cancel, Mariya A Mayer, Henry Qazi, Lance L Munn, John M Tarbell\",\"doi\":\"10.3233/BIR-180203\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Previous studies have demonstrated that the glycosaminoglycans (GAGs) heparan sulfate (HS) and hyaluronic acid (HA) are mechanosensors for interstitial flow on cancer cells. The proteins that link the GAGs to the cancer cell for mechanotransduction, however, are not known.</p><p><strong>Objective: </strong>To assess whether the HS proteoglycan core proteins, Glypican-1 and Syndecan-1, or the HA receptor, CD44, provides the mechanical linkage to the cell.</p><p><strong>Methods: </strong>The highly metastatic renal carcinoma cell line (SN12L1) and its companion low metastatic cell line (SN12C) were analyzed by Western blot, siRNA, and a 3-dimensional interstitial flow migration assay.</p><p><strong>Results: </strong>There was significant elevation of Glypican-1 protein expression in the SN12L1 cells relative to the SN12C cells while there were no significant differences in Syndecan-1 or CD44. Knock down of Glypican-1 by siRNA completely blocked flow induced migration in SN12L1 cells. MAPK inhibitors also blocked flow induced migration in SN12L1 cells.</p><p><strong>Conclusions: </strong>Glypican-1 provides the mechanical linkage from HS (the flow sensor) to the SN12L1 cell where mechanotransduction leading to the enhancement of migration (metastasis) occurs. MAPKs downstream of Glypican-1 propagate the signal. The HS, Glypican-1, MAPK signaling axis suggests opportunities for pharmaceutical intervention.</p>\",\"PeriodicalId\":9167,\"journal\":{\"name\":\"Biorheology\",\"volume\":\" \",\"pages\":\"151-161\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.3233/BIR-180203\",\"citationCount\":\"13\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biorheology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3233/BIR-180203\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biorheology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3233/BIR-180203","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOPHYSICS","Score":null,"Total":0}
The cancer cell glycocalyx proteoglycan Glypican-1 mediates interstitial flow mechanotransduction to enhance cell migration and metastasis.
Background: Previous studies have demonstrated that the glycosaminoglycans (GAGs) heparan sulfate (HS) and hyaluronic acid (HA) are mechanosensors for interstitial flow on cancer cells. The proteins that link the GAGs to the cancer cell for mechanotransduction, however, are not known.
Objective: To assess whether the HS proteoglycan core proteins, Glypican-1 and Syndecan-1, or the HA receptor, CD44, provides the mechanical linkage to the cell.
Methods: The highly metastatic renal carcinoma cell line (SN12L1) and its companion low metastatic cell line (SN12C) were analyzed by Western blot, siRNA, and a 3-dimensional interstitial flow migration assay.
Results: There was significant elevation of Glypican-1 protein expression in the SN12L1 cells relative to the SN12C cells while there were no significant differences in Syndecan-1 or CD44. Knock down of Glypican-1 by siRNA completely blocked flow induced migration in SN12L1 cells. MAPK inhibitors also blocked flow induced migration in SN12L1 cells.
Conclusions: Glypican-1 provides the mechanical linkage from HS (the flow sensor) to the SN12L1 cell where mechanotransduction leading to the enhancement of migration (metastasis) occurs. MAPKs downstream of Glypican-1 propagate the signal. The HS, Glypican-1, MAPK signaling axis suggests opportunities for pharmaceutical intervention.
期刊介绍：
Biorheology is an international interdisciplinary journal that publishes research on the deformation and flow properties of biological systems or materials. It is the aim of the editors and publishers of Biorheology to bring together contributions from those working in various fields of biorheological research from all over the world. A diverse editorial board with broad international representation provides guidance and expertise in wide-ranging applications of rheological methods to biological systems and materials.
The scope of papers solicited by Biorheology extends to systems at different levels of organization that have never been studied before, or, if studied previously, have either never been analyzed in terms of their rheological properties or have not been studied from the point of view of the rheological matching between their structural and functional properties. This biorheological approach applies in particular to molecular studies where changes of physical properties and conformation are investigated without reference to how the process actually takes place, how the forces generated are matched to the properties of the structures and environment concerned, proper time scales, or what structures or strength of structures are required.
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