Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite initial responsiveness, 80% of EOC patients recur and present with chemoresistant and a more aggressive disease. This suggests an underlying biology that results in a modified recurrent disease, which is distinct from...
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| Format: | Online |
| Language: | English |
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Blackwell Publishing Ltd
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892380/ |
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pubmed-3892380 |
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pubmed-38923802014-01-22 Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment Craveiro, Vinicius Yang-Hartwich, Yang Holmberg, Jennie C Sumi, Natalia J Pizzonia, John Griffin, Brian Gill, Sabrina K Silasi, Dan-Arin Azodi, Masoud Rutherford, Thomas Alvero, Ayesha B Mor, Gil Cancer Biology Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite initial responsiveness, 80% of EOC patients recur and present with chemoresistant and a more aggressive disease. This suggests an underlying biology that results in a modified recurrent disease, which is distinct from the primary tumor. Unfortunately, the management of recurrent EOC is similar to primary disease and does not parallel the molecular changes that may have occurred during the process of rebuilding the tumor. We describe the characterization of unique in vitro and in vivo ovarian cancer models to study the process of recurrence. The in vitro model consists of GFP+/CD44+/MyD88+ EOC stem cells and mCherry+/CD44−/MyD88− EOC cells. The in vivo model consists of mCherry+/CD44+/MyD88+ EOC cells injected intraperitoneally. Animals received four doses of Paclitaxel and response to treatment was monitored by in vivo imaging. Phenotype of primary and recurrent disease was characterized by quantitative polymerase chain reaction (qPCR) and Western blot analysis. Using the in vivo and in vitro models, we confirmed that chemotherapy enriched for CD44+/MyD88+ EOC stem cells. However, we observed that the surviving CD44+/MyD88+ EOC stem cells acquire a more aggressive phenotype characterized by chemoresistance and migratory potential. Our results highlight the mechanisms that may explain the phenotypic heterogeneity of recurrent EOC and emphasize the significant plasticity of ovarian cancer stem cells. The significance of our findings is the possibility of developing new venues to target the surviving CD44+/MyD88+ EOC stem cells as part of maintenance therapy and therefore preventing recurrence and metastasis, which are the main causes of mortality in patients with ovarian cancer. Blackwell Publishing Ltd 2013-12 2013-08-27 /pmc/articles/PMC3892380/ /pubmed/24403249 http://dx.doi.org/10.1002/cam4.115 Text en © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Craveiro, Vinicius Yang-Hartwich, Yang Holmberg, Jennie C Sumi, Natalia J Pizzonia, John Griffin, Brian Gill, Sabrina K Silasi, Dan-Arin Azodi, Masoud Rutherford, Thomas Alvero, Ayesha B Mor, Gil |
| spellingShingle |
Craveiro, Vinicius Yang-Hartwich, Yang Holmberg, Jennie C Sumi, Natalia J Pizzonia, John Griffin, Brian Gill, Sabrina K Silasi, Dan-Arin Azodi, Masoud Rutherford, Thomas Alvero, Ayesha B Mor, Gil Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| author_facet |
Craveiro, Vinicius Yang-Hartwich, Yang Holmberg, Jennie C Sumi, Natalia J Pizzonia, John Griffin, Brian Gill, Sabrina K Silasi, Dan-Arin Azodi, Masoud Rutherford, Thomas Alvero, Ayesha B Mor, Gil |
| author_sort |
Craveiro, Vinicius |
| title |
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| title_short |
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| title_full |
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| title_fullStr |
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| title_full_unstemmed |
Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment |
| title_sort |
phenotypic modifications in ovarian cancer stem cells following paclitaxel treatment |
| description |
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite initial responsiveness, 80% of EOC patients recur and present with chemoresistant and a more aggressive disease. This suggests an underlying biology that results in a modified recurrent disease, which is distinct from the primary tumor. Unfortunately, the management of recurrent EOC is similar to primary disease and does not parallel the molecular changes that may have occurred during the process of rebuilding the tumor. We describe the characterization of unique in vitro and in vivo ovarian cancer models to study the process of recurrence. The in vitro model consists of GFP+/CD44+/MyD88+ EOC stem cells and mCherry+/CD44−/MyD88− EOC cells. The in vivo model consists of mCherry+/CD44+/MyD88+ EOC cells injected intraperitoneally. Animals received four doses of Paclitaxel and response to treatment was monitored by in vivo imaging. Phenotype of primary and recurrent disease was characterized by quantitative polymerase chain reaction (qPCR) and Western blot analysis. Using the in vivo and in vitro models, we confirmed that chemotherapy enriched for CD44+/MyD88+ EOC stem cells. However, we observed that the surviving CD44+/MyD88+ EOC stem cells acquire a more aggressive phenotype characterized by chemoresistance and migratory potential. Our results highlight the mechanisms that may explain the phenotypic heterogeneity of recurrent EOC and emphasize the significant plasticity of ovarian cancer stem cells. The significance of our findings is the possibility of developing new venues to target the surviving CD44+/MyD88+ EOC stem cells as part of maintenance therapy and therefore preventing recurrence and metastasis, which are the main causes of mortality in patients with ovarian cancer. |
| publisher |
Blackwell Publishing Ltd |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892380/ |
| _version_ |
1612047657328443392 |