Eradication of chemotherapy‐resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of <i>clostridium perfringens</i> enterotoxin

Casagrande, Francesca; Cocco, Emiliano; Bellone, Stefania; Richter, C.; Bellone, Marta; Todeschini, Paola; Siegel, Eric R.; Varughese, Joyce; Arin-Silasi, Dan; Azodi, Masoud; Rutherford, Thomas J.; Pecorelli, Sërgio; Schwartz, Peter E.; Santin, Alessandro D.

doi:10.1002/cncr.26215

Cited by 63 publications

(61 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8,10,38 In addition, CD44þ cells are resistant to chemotherapy and are able to survive treatment with conventional drugs such as carboplatin and paclitaxel. 39 The findings described in this study are in support of the hypothesis that the CSCs are significant players in chemoresistance. In this model, chemotherapy only targets ovarian cancer cells but has no effect on the CSCs.…”

Section: Discussionsupporting

confidence: 86%

High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer

et al. 2013

View full text Add to dashboard Cite

Objective: Epithelial ovarian cancer (EOC) cells with CD44 and CK19 coexpression may represent a subset of ovarian cancer stem cells (OCSCs). This study was conducted to evaluate the correlation of the frequency of putative OCSCs (CD44 þ CK19 þ OCSCs) with the clinicopathologic features and the prognostic value in patients with recurrent advanced stage EOC. Methods: A retrospective study was carried out on 33 patients with EOC and a uniformly treated tissue microarray was constructed. A multiplexed, immunofluorescence-based method of automated in situ quantitative measurement of protein analysis was used for evaluation of the frequency or density of CD44 þ CK19 þ OCSCs in EOC. Results: The mean follow-up time was 42.8 + 27.1 months. High frequency of EOC cells with CD44þ or CD44þ/CK19þ was associated with chemoresistance (P ¼ .033 and P ¼ .02, respectively). Using K-M analysis with log-rank test, a high frequency of putative OCSCs was associated with short disease-free interval (7.9 months vs 20.9 months, P ¼ .019). In univariable analysis, the frequency of OCSCs, International Federation of Gynecology and Obstetrics stage and residual tumor volume were significant predictor variables and were entered into multivariable analysis (P ¼ .019, .037, and .005, respectively). Although no independent significant predictor was found, the frequency of putative OCSCs was the most promising predictor variable compared with the other 2 variables (hazard ratio ¼ 2.344, P ¼ .052). Conclusion: Our findings suggest that high frequency of OCSCs (CD44þ and CK19þ) in epithelial ovarian tumors correlates with short progression-free intervals.

show abstract

Section: Discussionsupporting

confidence: 86%

High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Therefore, targeting such antigens with mAbs or small molecules also may affect the normal tissues that express these antigens (48,49). However, with few exceptions (50), the postpartum expression of ROR1 seems restricted to cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Cui

Lai

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

166

156

View full text Add to dashboard Cite

Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1 + ) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1 Neg ) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1 + cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.ROR1 | ovarian cancer stem cell | monoclonal antibody | PDX mice model

show abstract

“…The analogues were screened against two clones of chemoresistant OCSCs (OCSC1 and OCSC2), which have demonstrated resistance to a variety of chemotherapeutic agents and thus represent the therapeutically relevant ovarian cancer cell subtype (9,(38)(39)(40). The efficacy of each analogue was based on its IC 50 .…”

Section: Identification Of Trx-e-002 As a Potent Inducer Of Ocsc Deathmentioning

confidence: 99%

TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo

Alvero

Heaton²,

Lima

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells.

show abstract

Eradication of chemotherapy‐resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of clostridium perfringens enterotoxin

Cited by 63 publications

References 23 publications

High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer

High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer

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

TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo

Contact Info

Product

Resources

About