Expression of cancer stem cell markers CD24, EPHA1 and CD9 and their correlation with clinical outcome in epithelial ovarian tumours

Nagare, Rohit P.; Sneha, Smarakan; Sidhanth, Chirukandath; Roopa, S; Murhekar, Kanchan; Sundersingh, Shirley; Swaminathan, Rajaraman; Sridevi, V.; Ganesan, Trivadi S.

doi:10.3233/cbm-201463

Cited by 14 publications

(20 citation statements)

References 33 publications

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“…Our results identify that in the setting of an altered microbiome, response to platinum chemotherapy is reduced and populations of chemo-resistance cancer stem cells are increased through tumorsphere initiation frequency and transcriptional reprogramming to an increased cancer stem cell-like state. The relationship between enhanced populations of cancer stem cells and platinum resistance in EOC is well-documented in the literature (28,45,48,(51)(52)(53)(54). Specifically, we identified SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 as being significantly upregulated in ID8 tumors of the ABX group over the control H 2 O group.…”

Section: Discussionmentioning

confidence: 62%

“…Specifically, we identified SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 as being significantly upregulated in ID8 tumors of the ABX group over the control H 2 O group. Many of these genes are markers of pluripotency and regulation as well as markers of long-term stemness (39,40,(42)(43)(44)(45). SALL1 interacts with NANOG a well-established pluripotency transcription factor, to suppress differentiation (44).…”

Section: Discussionmentioning

confidence: 99%

“…Genes commonly associated with cancer stem cell signatures were also increased in the ABX treatment group compared to the H 2 O control group such as SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 genes. SHOX2 and GATA5 genes that promote cell differentiation were also significantly 10 decreased(Figure C)(39)(40)(41)(42)(43)(44)(45)(46). Upon KEGG pathway analysis of genes with a p-value <0.01 in the ABX Placebo group vs. the H 2 O Placebo group, multiple signaling pathways were implicated including PI3-Akt, MAPK, WNT, and Hedgehog(Figure 5 D)(47)(48)(49)).As we observed increased stem cell markers based on RNAseq of tumors, we performed tumorsphere assays to assess stem cell frequency in tumors from H 2 O and ABX treated mice without and with cisplatin.…”

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confidence: 99%

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Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Chambers

Esakov

Braley

et al. 2020

Preprint

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Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy (cytoreductive surgery and platinum-taxane chemotherapy), up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections. We assessed whether antibiotics would impact growth of EOC and sensitivity to cisplatin in murine models. Murine ID8 or ID8-VEGF EOC that were injected intraperitoneally exhibited accelerated growth and augmented cisplatin resistance following treatment with antibiotics (ABX) in both C57 BL/6J and NSG mice, indicating this effect was independent of an intact immune system. While antibiotics are critical for the care of the patient, they profoundly impacted the microbiome. RNAseq analysis of ID8 tumors from the NSG ABX groups showed enrichment of multiple cell proliferation and stem cell pathways, and increased expression of common stem cell genes such as SOX2, WNT and PAX2. The cancer stem cell population was increased with antibiotic treatment and further augmented by cisplatin treatment. Collectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Chambers

Esakov

Braley

et al. 2020

Preprint

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“…Our results identify that in the setting of an altered microbiome, response to platinum chemotherapy is reduced and populations of chemo-resistance cancer stem cells are increased through tumorsphere initiation frequency and transcriptional reprogramming to an increased cancer stem cell-like state. The relationship between enhanced populations of cancer stem cells and platinum resistance in EOC is well-documented in the literature (28,45,48,(51)(52)(53)(54). Speci cally, we identi ed SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 as being signi cantly upregulated in ID8 tumors of the ABX group over the control H 2 O group.…”

Section: Discussionmentioning

confidence: 70%

“…SHOX2 and GATA5 genes that promote cell differentiation were also signi cantly decreased (Fig. 5C) (39)(40)(41)(42)(43)(44)(45)(46). Upon KEGG pathway analysis of genes with a p-value < 0.01 in the ABX Placebo group vs. the H 2 O Placebo group, multiple signaling pathways were implicated including PI3-Akt, MAPK, WNT, and Hedgehog (Fig.…”

Section: Abx Treatment Does Not Signi Cantly Alter Id8 or Id8-vegf Eomentioning

confidence: 94%

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Chambers¹,

Esakov

Braley

et al. 2020

Preprint

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Background: Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents. Experimental Design: We assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given either metronidazole, ampicillin, vancomycin, and neomycin (ABX) containing or control water for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to asses for microbial population effects over time.Results: Both immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of ABX treated tumor cells was also increased.Conclusion: Collectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.

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Oncogenic tetraspanins: Implications for metastasis, drug resistance, cancer stem cell maintenance and diagnosis of leading cancers in females

Marni

Chakraborty²,

Malla

2022

Gene Reports

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Expression of cancer stem cell markers CD24, EPHA1 and CD9 and their correlation with clinical outcome in epithelial ovarian tumours

Cited by 14 publications

References 33 publications

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Oncogenic tetraspanins: Implications for metastasis, drug resistance, cancer stem cell maintenance and diagnosis of leading cancers in females

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