PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations
<b>Background:</b> Ovarian cancer is the 7th most common cancer and 8th most mortal cancer among woman. The standard treatment includes cytoreduction surgery followed by chemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance. Decreased expression and...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-04-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/8/2053 |
id |
doaj-044fb1ef8d084d3490f93e6c7d2ffe18 |
---|---|
record_format |
Article |
spelling |
doaj-044fb1ef8d084d3490f93e6c7d2ffe182020-11-25T00:52:59ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-04-01208205310.3390/ijms20082053ijms20082053PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like PopulationsMonika Świerczewska0Karolina Sterzyńska1Karolina Wojtowicz2Dominika Kaźmierczak3Dariusz Iżycki4Michał Nowicki5Maciej Zabel6Radosław Januchowski7Department of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Cancer Immunology, Poznan University of Medical Sciences, Garbary 15 St., 61-866 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, PolandDepartment of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, Poland<b>Background:</b> Ovarian cancer is the 7th most common cancer and 8th most mortal cancer among woman. The standard treatment includes cytoreduction surgery followed by chemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance. Decreased expression and/or activity of protein phosphatases leads to increased signal transduction and development of drug resistance in cancer cells. <b>Methods:</b> Using sensitive (W1, A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine Phosphatase Receptor Type K (PTPRK) was performed at the mRNA (real-time PCR analysis) and protein level (Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues was determined by immunohistochemistry. <b>Results:</b> The results showed a decreased level of PTPRK expression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lower PTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation in primary as well as acquired resistance to cytotoxic drugs. <b>Conclusions:</b> These results provide important insights into the role of PTPRK in mechanism leading to drug resistance in ovarian cancer and has raised important questions about the role of imbalance in processes of phosphorylation and dephosphorylation.https://www.mdpi.com/1422-0067/20/8/2053protein tyrosine phosphatase receptor type K (PTPRK)cancer stem cells (CSCs)drug resistanceovarian cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Monika Świerczewska Karolina Sterzyńska Karolina Wojtowicz Dominika Kaźmierczak Dariusz Iżycki Michał Nowicki Maciej Zabel Radosław Januchowski |
spellingShingle |
Monika Świerczewska Karolina Sterzyńska Karolina Wojtowicz Dominika Kaźmierczak Dariusz Iżycki Michał Nowicki Maciej Zabel Radosław Januchowski PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations International Journal of Molecular Sciences protein tyrosine phosphatase receptor type K (PTPRK) cancer stem cells (CSCs) drug resistance ovarian cancer |
author_facet |
Monika Świerczewska Karolina Sterzyńska Karolina Wojtowicz Dominika Kaźmierczak Dariusz Iżycki Michał Nowicki Maciej Zabel Radosław Januchowski |
author_sort |
Monika Świerczewska |
title |
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations |
title_short |
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations |
title_full |
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations |
title_fullStr |
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations |
title_full_unstemmed |
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations |
title_sort |
ptprk expression is downregulated in drug resistant ovarian cancer cell lines, and especially in aldh1a1 positive cscs-like populations |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-04-01 |
description |
<b>Background:</b> Ovarian cancer is the 7th most common cancer and 8th most mortal cancer among woman. The standard treatment includes cytoreduction surgery followed by chemotherapy. Unfortunately, in most cases, after treatment, cancer develops drug resistance. Decreased expression and/or activity of protein phosphatases leads to increased signal transduction and development of drug resistance in cancer cells. <b>Methods:</b> Using sensitive (W1, A2780) and resistant ovarian cancer cell lines, the expression of Protein Tyrosine Phosphatase Receptor Type K (PTPRK) was performed at the mRNA (real-time PCR analysis) and protein level (Western blot, immunofluorescence analysis). The protein expression in ovarian cancer tissues was determined by immunohistochemistry. <b>Results:</b> The results showed a decreased level of PTPRK expression in ovarian cancer cell lines resistant to cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), topotecan (TOP), vincristine (VIN) and methotrexate (MTX). Additionally, the lower PTPRK expression was observed in Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) positive cancer stem cells (CSCs) population, suggesting the role of PTPRK downregulation in primary as well as acquired resistance to cytotoxic drugs. <b>Conclusions:</b> These results provide important insights into the role of PTPRK in mechanism leading to drug resistance in ovarian cancer and has raised important questions about the role of imbalance in processes of phosphorylation and dephosphorylation. |
topic |
protein tyrosine phosphatase receptor type K (PTPRK) cancer stem cells (CSCs) drug resistance ovarian cancer |
url |
https://www.mdpi.com/1422-0067/20/8/2053 |
work_keys_str_mv |
AT monikaswierczewska ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT karolinasterzynska ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT karolinawojtowicz ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT dominikakazmierczak ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT dariuszizycki ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT michałnowicki ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT maciejzabel ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations AT radosławjanuchowski ptprkexpressionisdownregulatedindrugresistantovariancancercelllinesandespeciallyinaldh1a1positivecscslikepopulations |
_version_ |
1725239879022936064 |