Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Epithelial ovarian cancer is a highly lethal gynecological malignancy that is characterized by the early development of disseminated metastasis. Though ovarian cancer has been generally considered to preferentially metastasize via direct transcoelomic dissemination instead of the hematogenous route, emerging evidence has indicated that the hematogenous spread of cancer cells plays a larger role in ovarian cancer metastasis than previously thought. Considering the distinctive biology of ovarian cancer, an in-depth understanding of the biological and molecular mechanisms that drive metastasis is critical for developing effective therapeutic strategies against this fatal disease. The recent “cancer stem cell theory” postulates that cancer stem cells are principally responsible for tumor initiation, metastasis, and chemotherapy resistance. Even though the hallmarks of ovarian cancer stem cells have not yet been completely elucidated, metastasized ovarian cancer cells, which have a high degree of chemoresistance, seem to manifest cancer stem cell properties and play a key role during relapse at metastatic sites. Herein, we review our current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches.

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HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

Bioscience Reports ◽

10.1042/bsr20180829 ◽

2019 ◽

Vol 39 (3) ◽

Cited By ~ 1

Author(s):

Wenxiang Wang ◽

Yuxia Gao ◽

Jing Hai ◽

Jing Yang ◽

Shufeng Duan

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Drug Sensitivity ◽

Ovarian Cancer Cells ◽

Her2 Overexpression ◽

Her2 Positive ◽

Ovarian Cancer Stem Cells

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24− population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.

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Cancer Stem Cells and Epithelial Ovarian Cancer

Journal of Oncology ◽

10.1155/2010/105269 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Sheetal Dyall ◽

Simon A. Gayther ◽

Dimitra Dafou

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

Epithelial Ovarian Cancer ◽

Primary Tumour ◽

Cellular Level ◽

Small Population ◽

Novel Target

The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs), or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

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IQGAP1 Is Involved in Enhanced Aggressive Behavior of Epithelial Ovarian Cancer Stem Cell-Like Cells During Differentiation

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000394 ◽

2015 ◽

Vol 25 (4) ◽

pp. 559-565 ◽

Cited By ~ 6

Author(s):

Lu Huang ◽

Shanshan Xu ◽

Dongxiao Hu ◽

Weiguo Lu ◽

Xing Xie ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

Messenger Rna ◽

De Novo ◽

Invasion And Metastasis ◽

Spheroid Culture ◽

Interfering Rna

BackgroundWide metastasis is one of characteristics of ovarian cancer. Cancer stem cells, as a source in cancer invasion and metastasis, possess powerful potential of differentiation. Scaffolding IQ domain GTPase-activating protein 1 (IQGAP1) plays a key role in the invasion and metastasis of cancer cells, but IQGAP1’s role in cancer stem cells including ovarian cancer was unclear.MethodsSpheroid culture with serum-free medium was used for enriching ovarian cancer stem cell-like cells (CSC-LCs) from 3AO cell line, and a medium with 10% fetal bovine serum was used to induce the differentiation of CSC-LCs. Immunofluorescence was for detecting the stem markers OCT4 and SOX2. The quantitative real-time-polymerase chain reaction and Western blotting were performed to determine the messenger RNA and protein expression of IQGAP1, respectively. The capacity of cell invasion was evaluated by transwell chamber assay.ResultsOvarian CSC-LCs obtained through spheroid culture showed irregularly elongated appearance, CD24 negative, and OCT4 and SOX2 positive. IQGAP1 expression was decreased in ovarian CSC-LCs compared with parental 3AO cells, but increased de novo during the differentiation of CSC-LCs. Knockdown of IQGAP1 by specific small interfering RNA remarkably weakened invasion capacity of 2-day differentiated ovarian CSC-LCs.ConclusionsIncreased IQGAP1 expression during the differentiation of CSC-LCs is involved in an aggressive cell behavior, which may contribute to metastasis of ovarian cancer.

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Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

10.21236/ada574853 ◽

2012 ◽

Author(s):

David W. Schomberg

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Hormone Receptor ◽

Follicle Stimulating Hormone ◽

Stem Cell Markers ◽

Ovarian Cancer Stem Cells ◽

Cell Markers ◽

Novel Approach

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Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

10.21236/ada601386 ◽

2013 ◽

Author(s):

David W. Schomberg

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Hormone Receptor ◽

Follicle Stimulating Hormone ◽

Stem Cell Markers ◽

Ovarian Cancer Stem Cells ◽

Cell Markers ◽

Novel Approach

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T1150 Role of Cyclooxygenase-2 in Cancer Stem Cell Biology and Effect of COX-2 Inhibitors in Anti-Cancer Therapy Targeting Cancer Stem Cells

Gastroenterology ◽

10.1016/s0016-5085(10)62305-0 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-499

Author(s):

Masahiko Tsujii ◽

Jumpei Kondo ◽

Tomofumi Akasaka ◽

Ying Jin ◽

Yoshito Hayashi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cancer Stem Cell ◽

Cell Biology ◽

Stem Cell Biology ◽

Anti Cancer ◽

Cox 2 ◽

Cox 2 Inhibitors

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Stem Cells and Cancer Stem Cells: The Jekyll and Hyde Scenario and Their Implications in Stem Cell Therapy

Biomedicines ◽

10.3390/biomedicines9091245 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1245

Author(s):

Wan Safwani Wan Kamarul Zaman ◽

Asma Abdullah Nurul ◽

Fazlina Nordin

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Cell Therapy ◽

Cancer Cells ◽

Stem Cell Therapy ◽

Embryonic Stem ◽

Cancer Development ◽

Cancer Microenvironment ◽

Good And Evil

“Jekyll and Hyde” refers to persons with an unpredictably dual personality, who are battling between good and evil within themselves In this regard, even cells consist of good and evil counterparts. Normal stem cells (NSCs) and cancer stem cells (CSCs) are two types of cells that share some similar characteristics but have distinct functions that play a major role in physiological and pathophysiological development. In reality, NSCs such as the adult and embryonic stem cells, are the good cells and the ultimate treatment used in cell therapy. CSCs are the corrupted cells that are a subpopulation of cancer cells within the cancer microenvironment that grow into a massive tumour or malignancy that needs to be treated. Hence, understanding the connection between NSCs and CSCs is important not just in cancer development but also in their therapeutic implication, which is the focus of this review.

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