The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance

Jain, Srishti; Annett, Stephanie; Morgan, Maria P.; Robson, Tracy

doi:10.3390/ijms22084091

Cited by 16 publications

(17 citation statements)

References 130 publications

(132 reference statements)

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“…Most OC patients with recurrence after surgery and first-line chemotherapy are also resistant to second-line chemotherapy, which is a major clinical issue [ 65 , 66 , 67 ]. Growing evidence indicates that the nature of chemoresistance in OC is furthered by the existing subpopulations of drug-resistant OC cells [ 65 , 66 , 68 ]. Our data found that overexpression of several mitotic KIFs manifests a correlation with chemoresistance against drugs currently used in first- and second-line, thereby creating a functional connection between overexpressed mitotic KIFs and drug-resistant OC cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…These drug-resistant OC cells may be derived from ovarian cancer stem cells (OCSCs), which can undergo genetic or epigenetic changes to generate microenvironmental immunosuppression and intertumoral heterogeneity (ITH) by dynamically interacting with the immunosurveillance and tumor microenvironment [ 68 ]. Most OC patients with tumor-infiltrating lymphocytes (TILs) are supposed to profit from a better outcome [ 68 ]; e.g., it was reported that OC patients whose tumors have intratumoral TILs experienced longer OS and PFS than patients whose tumors lacked TILs [ 69 ]. However, our immune infiltration analysis indicated that overexpression of mitotic KIFs was rarely correlated with almost all types of immune cells, including CD4+T cells, CD8+T cells, B cells, and macrophages, implying that OC cells with high expression levels of mitotic KIFs may generate a favorable immunosuppressive microenvironment to escape the immunosurveillance.…”

Section: Discussionmentioning

confidence: 99%

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Identifying Mitotic Kinesins as Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses

et al. 2022

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Ovarian cancer (OC) is characterized by late-stage presentation, chemoresistance, and poor survival. Evaluating the prognosis of OC patients via effective biomarkers is essential to manage OC progression and to improve survival; however, it has been barely established. Here, we intend to identify differentially expressed genes (DEGs) as potential prognostic biomarkers of OC via bioinformatic analyses. Initially, a total of thirteen DEGs were extracted from different public databases as candidates. The expression of KIF20A, one of the DEGs, was correlated with a worse outcome of OC patients. The functional correlation of the DEGs with mitosis and the prognostic value of KIF20A imply a high correlation between mitotic kinesins (KIFs) and OC development. Finally, we found that KIF20A, together with the other nine mitotic KIFs (4A, 11, 14, 15, 18A, 18B, 23, C1, and2C) were upregulated and activated in OC tissues. Among the ten, seven overexpressed mitotic KIFs (11, 14, 18B, 20A, 23, and C1) were correlated with unfavorable clinical prognosis. Moreover, KIF20A and KIF23 overexpression was associated with worse prognosis in OC patients treated with platinum/taxol chemotherapy, while OCs overexpressing mitotic KIFs (11, 15, 18B, and C1) were resistant to MAPK pathway inhibitors. In conclusion, worse outcomes of OC patients were correlated with overexpression of several mitotic KIFs, which may serve both as prognostic biomarkers and therapeutic targets for OC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identifying Mitotic Kinesins as Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses

et al. 2022

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“…The inhibition of the JAK2/STAT3 pathway in OC results in a loss of cancer stemness and reduced tumor growth [ 85 ]. The inhibition of the over-expressed JAK2/STAT3 pathway in patient-derived CD24+ OCSCs correlated with a better survival of OC patients [ 86 ]. The CD24 molecule may also regulate NANOG and OCT4 expression, thus stimulating tumor growth and resistance to chemotherapy.…”

Section: Ovarian Cancer Stem Cells (Ocscs)—markersmentioning

confidence: 99%

Cancer Stem Cells in Ovarian Cancer—A Source of Tumor Success and a Challenging Target for Novel Therapies

Wilczyński

Paradowska

2022

IJMS

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Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy.

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“…Thanks to experiments performed recently to shed some light on the role of CSCs. It seems that presence of CSCs in TME results in immune evasion and immunosuppression [ 89 ]. The CSCs are able to induce drug resistance feature of tumor cells.…”

Section: Cancer Stem Cells In Oncologymentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance

Cited by 16 publications

References 130 publications

Identifying Mitotic Kinesins as Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses

Identifying Mitotic Kinesins as Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses

Cancer Stem Cells in Ovarian Cancer—A Source of Tumor Success and a Challenging Target for Novel Therapies

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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