Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells
The interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial–mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-12-01
|
| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428320979438 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849709860711563264 |
|---|---|
| author | Natalia Ospina-Muñoz Jean-Paul Vernot |
| author_facet | Natalia Ospina-Muñoz Jean-Paul Vernot |
| author_sort | Natalia Ospina-Muñoz |
| collection | DOAJ |
| description | The interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial–mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces the formation of larger tumorspheres in Michigan Cancer Foundation-7 (MCF-7) cells, suggesting cancer stem cell enrichment. In this work, we aimed to study the phenotypic and functional characteristics of the cells present within the tumorspheres of MCF-7 cells previously treated with interleukin-8. MCF-7 cells treated for 5 days or not with this cytokine were further cultivated in ultralow attachment plates for another 5 days to allow tumorspheres formation. We showed that the enhanced sphere formation by MCF-7 cells was not a consequence of higher cell proliferation by interleukin-8 stimulation. Despite maintaining an epithelial–mesenchymal transition phenotype with the presence of epithelial and mesenchymal markers, basic stemness properties were impaired in tumorspheres and in those treated with interleukin-8, while others were increased. Self-renewal capacity was increased in interleukin-8-treated cells only in the first generation of tumorspheres but was not sustained in consecutive assays. Accordingly, self-renewal and reprogramming gene expression, differentiation capacity to adipocytes, and clonogenicity were also impaired. We showed also that tumorspheres were enriched in differentiated luminal cells (EpCAM+/CD49f−). Nevertheless, cells were more quiescent and maintain a partial epithelial–mesenchymal transition, consistent with their increased resistance to Paclitaxel and Doxorubicin. They also presented higher migration and interleukin-8-directed invasion. Therefore, the breast cancer cell line MCF-7, having a low stemness index, might partially acquire some stem-like cell attributes after interleukin-8 stimulation, increasing its aggressiveness. |
| format | Article |
| id | doaj-art-2d818905c58e48638a5704fa5edd8a97 |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-2d818905c58e48638a5704fa5edd8a972025-08-20T03:15:08ZengSAGE PublishingTumor Biology1423-03802020-12-014210.1177/1010428320979438Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cellsNatalia Ospina-Muñoz0Jean-Paul Vernot1Cellular and Molecular Physiology Group, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, DC, ColombiaInstituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, DC, ColombiaThe interleukin-8 is an important regulator of the tumor microenvironment, promoting the epithelial–mesenchymal transition and the acquisition of stem-like cell properties in cancer cells. The tumorsphere-formation assay has been used for the identification of cancer stem cell. Interleukin-8 induces the formation of larger tumorspheres in Michigan Cancer Foundation-7 (MCF-7) cells, suggesting cancer stem cell enrichment. In this work, we aimed to study the phenotypic and functional characteristics of the cells present within the tumorspheres of MCF-7 cells previously treated with interleukin-8. MCF-7 cells treated for 5 days or not with this cytokine were further cultivated in ultralow attachment plates for another 5 days to allow tumorspheres formation. We showed that the enhanced sphere formation by MCF-7 cells was not a consequence of higher cell proliferation by interleukin-8 stimulation. Despite maintaining an epithelial–mesenchymal transition phenotype with the presence of epithelial and mesenchymal markers, basic stemness properties were impaired in tumorspheres and in those treated with interleukin-8, while others were increased. Self-renewal capacity was increased in interleukin-8-treated cells only in the first generation of tumorspheres but was not sustained in consecutive assays. Accordingly, self-renewal and reprogramming gene expression, differentiation capacity to adipocytes, and clonogenicity were also impaired. We showed also that tumorspheres were enriched in differentiated luminal cells (EpCAM+/CD49f−). Nevertheless, cells were more quiescent and maintain a partial epithelial–mesenchymal transition, consistent with their increased resistance to Paclitaxel and Doxorubicin. They also presented higher migration and interleukin-8-directed invasion. Therefore, the breast cancer cell line MCF-7, having a low stemness index, might partially acquire some stem-like cell attributes after interleukin-8 stimulation, increasing its aggressiveness.https://doi.org/10.1177/1010428320979438 |
| spellingShingle | Natalia Ospina-Muñoz Jean-Paul Vernot Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells Tumor Biology |
| title | Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells |
| title_full | Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells |
| title_fullStr | Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells |
| title_full_unstemmed | Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells |
| title_short | Partial acquisition of stemness properties in tumorspheres obtained from interleukin-8-treated MCF-7 cells |
| title_sort | partial acquisition of stemness properties in tumorspheres obtained from interleukin 8 treated mcf 7 cells |
| url | https://doi.org/10.1177/1010428320979438 |
| work_keys_str_mv | AT nataliaospinamunoz partialacquisitionofstemnesspropertiesintumorspheresobtainedfrominterleukin8treatedmcf7cells AT jeanpaulvernot partialacquisitionofstemnesspropertiesintumorspheresobtainedfrominterleukin8treatedmcf7cells |