Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells
CD44v6-containing isoforms are frequently de novo expressed in gastric cancer (GC). Whether CD44v6 has a central role in GC transformation and/or progression, whether it conditions response to therapy or whether it is only a bystander marker is still not known. Therefore, we aimed to clarify the rol...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/4/858 |
| _version_ | 1797571693451935744 |
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| author | Carla Pereira Daniel Ferreira Nuno Mendes Pedro L. Granja Gabriela M. Almeida Carla Oliveira |
| author_facet | Carla Pereira Daniel Ferreira Nuno Mendes Pedro L. Granja Gabriela M. Almeida Carla Oliveira |
| author_sort | Carla Pereira |
| collection | DOAJ |
| description | CD44v6-containing isoforms are frequently de novo expressed in gastric cancer (GC). Whether CD44v6 has a central role in GC transformation and/or progression, whether it conditions response to therapy or whether it is only a bystander marker is still not known. Therefore, we aimed to clarify the role of CD44v6 in GC. We generated GC isogenic cell lines stably expressing CD44s or CD44v6 and tested them for different cancer hallmarks and response to cisplatin, and we further confirmed our findings in cells that endogenously express CD44v6. No correlation between overexpression of CD44v6 and the tested cancer hallmarks was observed, suggesting CD44v6 is not a driver of GC progression. Upon cisplatin treatment, CD44v6+ cells survive better and have lower apoptosis levels than CD44v6− cells, possibly due to concomitant activation of STAT3 and P38. In co-culture experiments, we discovered that CD44v6+ cells are involved in GC cell overgrowth after cisplatin treatment. In conclusion, we show that CD44v6 expression increases cell survival in response to cisplatin treatment in GC cells and that these cells override CD44v6-negative cells after cisplatin-treatment. This suggests that tumor expression of CD44v6-containing variants may condition the outcome of GC patients treated with chemotherapy. |
| first_indexed | 2024-03-10T20:44:08Z |
| format | Article |
| id | doaj.art-9e75e5fa37f74dc4ac7abd6cb7fcd853 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:44:08Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9e75e5fa37f74dc4ac7abd6cb7fcd8532023-11-19T20:28:50ZengMDPI AGCancers2072-66942020-04-0112485810.3390/cancers12040858Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer CellsCarla Pereira0Daniel Ferreira1Nuno Mendes2Pedro L. Granja3Gabriela M. Almeida4Carla Oliveira5i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugali3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, PortugalCD44v6-containing isoforms are frequently de novo expressed in gastric cancer (GC). Whether CD44v6 has a central role in GC transformation and/or progression, whether it conditions response to therapy or whether it is only a bystander marker is still not known. Therefore, we aimed to clarify the role of CD44v6 in GC. We generated GC isogenic cell lines stably expressing CD44s or CD44v6 and tested them for different cancer hallmarks and response to cisplatin, and we further confirmed our findings in cells that endogenously express CD44v6. No correlation between overexpression of CD44v6 and the tested cancer hallmarks was observed, suggesting CD44v6 is not a driver of GC progression. Upon cisplatin treatment, CD44v6+ cells survive better and have lower apoptosis levels than CD44v6− cells, possibly due to concomitant activation of STAT3 and P38. In co-culture experiments, we discovered that CD44v6+ cells are involved in GC cell overgrowth after cisplatin treatment. In conclusion, we show that CD44v6 expression increases cell survival in response to cisplatin treatment in GC cells and that these cells override CD44v6-negative cells after cisplatin-treatment. This suggests that tumor expression of CD44v6-containing variants may condition the outcome of GC patients treated with chemotherapy.https://www.mdpi.com/2072-6694/12/4/858stomach cancerchemotherapyCD44 variantsapoptosiscell population dynamics |
| spellingShingle | Carla Pereira Daniel Ferreira Nuno Mendes Pedro L. Granja Gabriela M. Almeida Carla Oliveira Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells Cancers stomach cancer chemotherapy CD44 variants apoptosis cell population dynamics |
| title | Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells |
| title_full | Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells |
| title_fullStr | Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells |
| title_full_unstemmed | Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells |
| title_short | Expression of CD44v6-Containing Isoforms Influences Cisplatin Response in Gastric Cancer Cells |
| title_sort | expression of cd44v6 containing isoforms influences cisplatin response in gastric cancer cells |
| topic | stomach cancer chemotherapy CD44 variants apoptosis cell population dynamics |
| url | https://www.mdpi.com/2072-6694/12/4/858 |
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