Effect of ovulation IGF and HGF signaling on the oncogenesis of murine epithelial ovarian cancer cell ID8

Chu, Tang–Yuan; Chu, Sung‐Chao; Khine, Aye Aye; Chen, Pao-Chu; Lee, Ming-Hsun; Huang, Hsuan-Shun

doi:10.1016/j.yexcr.2022.113323

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…In conclusion, in this and early 26,27 studies, we have demonstrated that both IGF2 and HGF signals in FF are important for the malignant transformation of HGSC. FF‐IGF‐axis pathway is mainly associated with increased cell clonogenicity, supporting the stemness and clonal expansion activities essential for cell transformation.…”

Section: Discussionsupporting

confidence: 51%

“…24,25 A broad spectrum of cell transformation phenotypes, such as stemness, clonal expansion, anchorageindependent growth (AIG), migration, invasion, anoikis resistance, and peritoneal attachment, were all found to be enhanced by FF. 24,26 Besides the ROS, we have identified insulin-like growth factor (IGF2) and hepatocyte growth factor (HGF) as the essential oncogenic growth factors in FF. IGF2 associated with the IGF-axis proteins was abundantly present in FF.…”

Section: Introductionmentioning

confidence: 99%

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Insulin‐like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high‐grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects

Chu

Khine

et al. 2023

Molecular Carcinogenesis

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Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin‐like growth factor (IGF2) and hepatocyte growth factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high‐grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co‐injection model, we observed that FF co‐injection induced tumorigenesis of STIC‐mimicking cells, FE25. Co‐injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co‐injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring‐independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine‐protein kinase Met (cMET)/mitogen‐activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF‐IGF2 could mediate clonogenicity and stemness activities via the IGF‐1R/AKT/mammalian target of rapamycin and IGF‐1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF‐sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Insulin‐like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high‐grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects

Chu

Khine

et al. 2023

Molecular Carcinogenesis

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A simple, economical, and high-yield method for polyethylene glycol-based extraction of follicular and serum-derived extracellular vesicles

Khine,

Chen,

Chen

et al. 2024

Tzu Chi Medical Journal

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Objectives: The optimization of polyethylene glycol (PEG)-based extracellular vesicles (EVs) extraction from human follicular fluid (FF) and serum was investigated, and their functional analysis was confirmed. The PEG-based EV results were compared to the ExoQuick (ExoQ)-based EV. Materials and Methods: FF-EVs and serum-EVs were extracted by using different concentrations of PEG (8000). Nanoparticle tracking analysis was used to count the particles, and electron microscopy of EVs was performed for visualization. Exosomes were confirmed by the western blot analysis with exosome-specific markers. RNA and microRNA were extracted from exosomes and quantitative polymerase chain reaction analysis was performed. Fallopian tube epithelial (FTE) cells were used for the EV uptake experiment and an anchorage-independent growth test to confirm that extracted EVs harbor transformation activity. Results: The PEG 8% enriched method produced the highest yield and the lowest carry-over protein. Salt containing PEG 8% produced a higher yield than nonsalted PEG 8%. Overnight enrichment increased four times and 18 times for PEG 8% and ExoQ-based EV extraction from FF. For serum EV, the same overnight enrichment moderately increased yield for both PEG 8% and ExoQ methods. Less carry-over protein resulted in more EV-promoted transformation activity. Conclusion: This study overcomes the time-consuming, expensive, laborious, and complicated machine-dependent EV extraction methods. The study highlights that longer incubation time is needed for EV extraction from FF. PEG 8000-based EV extraction provided a higher yield and less carry-over protein than ExoQ-based EV extraction.

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Effect of ovulation IGF and HGF signaling on the oncogenesis of murine epithelial ovarian cancer cell ID8

Cited by 2 publications

References 33 publications

Insulin‐like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high‐grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects

Insulin‐like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high‐grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects

A simple, economical, and high-yield method for polyethylene glycol-based extraction of follicular and serum-derived extracellular vesicles

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