Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line
Abstract The remarkable biophysical properties of metastatic migrating cells, such as their exceptional motility and deformability, enable them to migrate through physical confinements created by neighboring cells or extracellular matrix. This study explores the adaptive responses of breast cancer (...
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Nature Portfolio
2025-05-01
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| author | Zain Nofal Philipp Malakhov Margarita Pustovalova Nawar Sakr Sergey Leonov |
| author_facet | Zain Nofal Philipp Malakhov Margarita Pustovalova Nawar Sakr Sergey Leonov |
| author_sort | Zain Nofal |
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| description | Abstract The remarkable biophysical properties of metastatic migrating cells, such as their exceptional motility and deformability, enable them to migrate through physical confinements created by neighboring cells or extracellular matrix. This study explores the adaptive responses of breast cancer (BC) cell sublines derived from the highly aggressive, metastatic triple-negative MDA-MB-231 and the non-metastatic MCF7 human BC cell lines, after undergoing three rounds of confined migration (CM) stress. Our findings demonstrate that CM elicits common and cell-type specific adaptive responses in BC cell sublines. In particular, both cell sublines exhibit a similar enhancement of clonogenicity and nanoparticle (NP) uptake activity, indicating tumorigenic potential. We have, for the first time, shown that stimulation with CM induces a hybrid epithelial-to-mesenchymal transition (EMT) phenotype of MDA-MB-231 cells. This transition is characterized by a significant rise in the expression of stage-specific embryonic antigen-4 (SSEA4), alongside a substantial decline in the population of CD133+ cells and a marked reduction in Ki67 expression in the MDA-MB-231-derived subline following Cis-Platin treatment. These changes are likely associated with heightened resistance of this subline to cisplatin. In contrast, CM induces far fewer such alterations in the MCF7-derived counterpart with a notable increase of CD133+ population, which seems to be insufficient to change cell susceptibility to cisplatin exposure. This study contributes to our understanding of the adaptive mechanisms underlying metastasis and drug resistance in breast cancer, emphasizing the need for personalized approaches in cancer treatment that consider the heterogeneous responses of different cancer subtypes to environmental stresses. |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-e7d722f7a1e34750b41cda4910ba247f2025-08-20T01:51:39ZengNature PortfolioScientific Reports2045-23222025-05-0115111610.1038/s41598-025-99828-6Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell lineZain Nofal0Philipp Malakhov1Margarita Pustovalova2Nawar Sakr3Sergey Leonov4Institute of Future Biophysics, Moscow Institute of Physics and Technology, MIPT, PhystechInstitute of Future Biophysics, Moscow Institute of Physics and Technology, MIPT, PhystechInstitute of Future Biophysics, Moscow Institute of Physics and Technology, MIPT, PhystechFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesInstitute of Future Biophysics, Moscow Institute of Physics and Technology, MIPT, PhystechAbstract The remarkable biophysical properties of metastatic migrating cells, such as their exceptional motility and deformability, enable them to migrate through physical confinements created by neighboring cells or extracellular matrix. This study explores the adaptive responses of breast cancer (BC) cell sublines derived from the highly aggressive, metastatic triple-negative MDA-MB-231 and the non-metastatic MCF7 human BC cell lines, after undergoing three rounds of confined migration (CM) stress. Our findings demonstrate that CM elicits common and cell-type specific adaptive responses in BC cell sublines. In particular, both cell sublines exhibit a similar enhancement of clonogenicity and nanoparticle (NP) uptake activity, indicating tumorigenic potential. We have, for the first time, shown that stimulation with CM induces a hybrid epithelial-to-mesenchymal transition (EMT) phenotype of MDA-MB-231 cells. This transition is characterized by a significant rise in the expression of stage-specific embryonic antigen-4 (SSEA4), alongside a substantial decline in the population of CD133+ cells and a marked reduction in Ki67 expression in the MDA-MB-231-derived subline following Cis-Platin treatment. These changes are likely associated with heightened resistance of this subline to cisplatin. In contrast, CM induces far fewer such alterations in the MCF7-derived counterpart with a notable increase of CD133+ population, which seems to be insufficient to change cell susceptibility to cisplatin exposure. This study contributes to our understanding of the adaptive mechanisms underlying metastasis and drug resistance in breast cancer, emphasizing the need for personalized approaches in cancer treatment that consider the heterogeneous responses of different cancer subtypes to environmental stresses.https://doi.org/10.1038/s41598-025-99828-6Confined migrationBreast cancerStem cell markersCisplatin resistanceNano-particle endocytosis |
| spellingShingle | Zain Nofal Philipp Malakhov Margarita Pustovalova Nawar Sakr Sergey Leonov Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line Scientific Reports Confined migration Breast cancer Stem cell markers Cisplatin resistance Nano-particle endocytosis |
| title | Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line |
| title_full | Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line |
| title_fullStr | Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line |
| title_full_unstemmed | Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line |
| title_short | Recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside SSEA-4 expression, boosting clonogenicity and cisplatin resistance in TNBC cell line |
| title_sort | recurring cycles of deprivation of serum and migration in confined spaces augments ganglioside ssea 4 expression boosting clonogenicity and cisplatin resistance in tnbc cell line |
| topic | Confined migration Breast cancer Stem cell markers Cisplatin resistance Nano-particle endocytosis |
| url | https://doi.org/10.1038/s41598-025-99828-6 |
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