Abstract 3094: Estrogen receptor β agonist depletes ovarian cancer stem cells via repressing epithelial to mesenchymal transition

Within the ovarian cancer tumor microenvironment, cancer stem-like cells (CSC) interact with carcinoma associated mesenchymal stem/stromal cells (CA-MSC) through multiple secreted cytokines and growth factors. These paracrine interactions have been revealed to cause enrichment of CSC and their chemoprotection; however, it is still not known if platelet-derived growth factor (PDGF) signaling is involved in facilitating these responses. In order to probe this undiscovered bidirectional communication, we created a model of ovarian malignant ascites in the three-dimensional (3D) hanging drop heterospheroid array, with CSC and CA-MSC. We hypothesized that PDGF secretion by CA-MSC increases self-renewal, migration, epithelial to mesenchymal transition (EMT) and chemoresistance in ovarian CSC. Our results indicate that PDGF signaling in the CSC-MSC heterospheroids significantly increased stemness, metastatic potential and chemoresistance of CSC. Knockdown of PDGFB in MSC resulted in abrogation of these phenotypes in the heterospheroids. Our studies also reveal a cross-talk between PDGF and Hedgehog signaling in ovarian cancer. Overall, our data suggest that when the stromal signaling via PDGF to ovarian CSC is blocked in addition to chemotherapy pressure, the tumor cells are significantly more sensitive to chemotherapy. Our results emphasize the importance of disrupting the signals from the microenvironment to the tumor cells, in order to improve response rates. These findings may lead to the development of combination therapies targeting stromal signaling (such as PDGF and Hedgehog) that can abrogate the tumorigenic, metastatic and platinum resistant phenotypes of ovarian CSC through additional investigations.

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Abstract 4734: Inhibitory effects of metformin on epithelial-mesenchymal transition of CD44+/CD117+ ovarian cancer stem cells

10.1158/1538-7445.am2016-4734 ◽

2016 ◽

Author(s):

Gary G. Xiao ◽

Rongrong Zhang ◽

Ping Zhang ◽

Hong Wang ◽

Dongming Hou ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Epithelial Mesenchymal Transition ◽

Inhibitory Effects ◽

Ovarian Cancer Stem Cells ◽

Mesenchymal Transition

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The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽

10.3390/cancers13061239 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1239

Author(s):

Leila Jahangiri ◽

Tala Ishola ◽

Perla Pucci ◽

Ricky M. Trigg ◽

Joao Pereira ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Regulatory Networks ◽

Epithelial To Mesenchymal Transition ◽

Tumour Microenvironment ◽

Repair Capacity ◽

Mesenchymal Transition ◽

Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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