Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells
Podoplanin and CD44 are transmembrane glycoproteins involved in inflammation and cancer. In this paper, we report that podoplanin is coordinately expressed with the CD44 standard (CD44s) and variant (CD44v) isoforms in vivo—in hyperplastic skin after a pro-inflammatory stimulus with 12-<i>O<...
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2200 |
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| author | Lucía Montero-Montero Jaime Renart Andrés Ramírez Carmen Ramos Mariam Shamhood Rocío Jarcovsky Miguel Quintanilla Ester Martín-Villar |
| author_facet | Lucía Montero-Montero Jaime Renart Andrés Ramírez Carmen Ramos Mariam Shamhood Rocío Jarcovsky Miguel Quintanilla Ester Martín-Villar |
| author_sort | Lucía Montero-Montero |
| collection | DOAJ |
| description | Podoplanin and CD44 are transmembrane glycoproteins involved in inflammation and cancer. In this paper, we report that podoplanin is coordinately expressed with the CD44 standard (CD44s) and variant (CD44v) isoforms in vivo—in hyperplastic skin after a pro-inflammatory stimulus with 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA)—and in vitro—in cell lines representative of different stages of mouse-skin chemical carcinogenesis, as well as in human squamous carcinoma cell (SCC) lines. Moreover, we identify CD44v10 in the mouse-skin carcinogenesis model as the only CD44 variant isoform expressed in highly aggressive spindle carcinoma cell lines together with CD44s and podoplanin. We also characterized CD44v3-10, CD44v6-10 and CD44v8-10 as the major variant isoforms co-expressed with CD44s and podoplanin in human SCC cell lines. Immunofluorescence confocal microscopy experiments show that these CD44v isoforms colocalize with podoplanin at plasma membrane protrusions and cell–cell contacts of SCC cells, as previously reported for CD44s. Furthermore, CD44v isoforms colocalize with podoplanin in chemically induced mouse-skin SCCs in vivo. Co-immunoprecipitation experiments indicate that podoplanin physically binds to CD44v3-10, CD44v6-10 and CD44v8-10 isoforms, as well as to CD44s. Podoplanin–CD44 interaction is mediated by the transmembrane and cytosolic regions and is negatively modulated by glycosylation of the extracellular domain. These results point to a functional interplay of podoplanin with both CD44v and CD44s isoforms in SCCs and give insight into the regulation of the podoplanin–CD44 association. |
| first_indexed | 2024-03-09T06:06:13Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T06:06:13Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4cd2fd9b32784bddb767a21b08bdff892023-12-03T12:02:51ZengMDPI AGCells2073-44092020-09-01910220010.3390/cells9102200Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma CellsLucía Montero-Montero0Jaime Renart1Andrés Ramírez2Carmen Ramos3Mariam Shamhood4Rocío Jarcovsky5Miguel Quintanilla6Ester Martín-Villar7Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainDepartamento de Biotecnología—Instituto de Investigaciones Biosanitarias. Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria (UFV), 28223 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainInstituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)—Universidad Autónoma de Madrid (UAM), 28029 Madrid, SpainPodoplanin and CD44 are transmembrane glycoproteins involved in inflammation and cancer. In this paper, we report that podoplanin is coordinately expressed with the CD44 standard (CD44s) and variant (CD44v) isoforms in vivo—in hyperplastic skin after a pro-inflammatory stimulus with 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA)—and in vitro—in cell lines representative of different stages of mouse-skin chemical carcinogenesis, as well as in human squamous carcinoma cell (SCC) lines. Moreover, we identify CD44v10 in the mouse-skin carcinogenesis model as the only CD44 variant isoform expressed in highly aggressive spindle carcinoma cell lines together with CD44s and podoplanin. We also characterized CD44v3-10, CD44v6-10 and CD44v8-10 as the major variant isoforms co-expressed with CD44s and podoplanin in human SCC cell lines. Immunofluorescence confocal microscopy experiments show that these CD44v isoforms colocalize with podoplanin at plasma membrane protrusions and cell–cell contacts of SCC cells, as previously reported for CD44s. Furthermore, CD44v isoforms colocalize with podoplanin in chemically induced mouse-skin SCCs in vivo. Co-immunoprecipitation experiments indicate that podoplanin physically binds to CD44v3-10, CD44v6-10 and CD44v8-10 isoforms, as well as to CD44s. Podoplanin–CD44 interaction is mediated by the transmembrane and cytosolic regions and is negatively modulated by glycosylation of the extracellular domain. These results point to a functional interplay of podoplanin with both CD44v and CD44s isoforms in SCCs and give insight into the regulation of the podoplanin–CD44 association.https://www.mdpi.com/2073-4409/9/10/2200podoplaninCD44sCD44vsquamous carcinoma cellsprotein–protein interaction |
| spellingShingle | Lucía Montero-Montero Jaime Renart Andrés Ramírez Carmen Ramos Mariam Shamhood Rocío Jarcovsky Miguel Quintanilla Ester Martín-Villar Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells Cells podoplanin CD44s CD44v squamous carcinoma cells protein–protein interaction |
| title | Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells |
| title_full | Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells |
| title_fullStr | Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells |
| title_full_unstemmed | Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells |
| title_short | Interplay between Podoplanin, CD44s and CD44v in Squamous Carcinoma Cells |
| title_sort | interplay between podoplanin cd44s and cd44v in squamous carcinoma cells |
| topic | podoplanin CD44s CD44v squamous carcinoma cells protein–protein interaction |
| url | https://www.mdpi.com/2073-4409/9/10/2200 |
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