Haemoglobin in pelvic fluid rescues Fallopian tube epithelial cells from reactive oxygen species stress and apoptosis

Huang, Hsuan-Shun; Hsu, Che-Fang; Chu, Sung‐Chao; Chen, Pao-Chu; Ding, Dah-Ching; Chang, Meng-Ya; Chu, Tang–Yuan

doi:10.1002/path.4807

Cited by 32 publications

(43 citation statements)

References 32 publications

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“…This lesion shares identical p53 mutations and other genomic changes with HGSC, but lacks excessive cell proliferation (16). p53 signature is seen predominantly in continuity with STIC, localizes to the same (fimbria) region as STIC and shares preneoplastic properties with HGSC including p53 mutations (5,17). p53 signature is frequently identified in serous cancer (66%) and may promote p53-driven preneoplastic transformation (12).…”

Section: Histopathology Of Precursor Lesionsmentioning

confidence: 99%

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

et al. 2017

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Abstract. The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC). A series of morphological changes from normal fallopian epithelium to preneoplastic to neoplastic lesions were concomitant with the multistep accumulation of molecular and genetic alterations. Recent studies provide a stepwise progression of fallopian tubal epithelium to precursor lesions to carcinoma, with the aid of a 'secretory cell-SCE-SCOUT-p53 signature-STIC-HGSC sequence' model. Immunohistochemical markers, including p53, STMN1, EZH2, CCNE1, Ki67 and γ-H2AX, were gradua lly increased during the SCOUT-p53 signature-STIC-HGSC sequence. Conversely, PAX2 expression was decreased during the early phase of SCOUT development. Potential genes and proteins are involved in the evolutionary trajectory of the precursor-cancer lineage model. In the present review we examined detailed aspects of the molecular changes involved in malignant transformation from fallopian tube epithelium to HGSC. A precursor condition originating in 'field cancerization' may gain a growth advantage, leading to HGSC.

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Section: Histopathology Of Precursor Lesionsmentioning

confidence: 99%

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

et al. 2017

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“…In studying the transformation of the human fimbrial epithelial secretory cell, the presumed cell-of-origin of HGSOC, studies have used immortalized fimbrial epithelial cells for transformation [8,28,29] and showed clonal expansion and stemness activation on these p53/Rb-deficient FTEC. Although these studies clearly indicated fallopian tube epithelial cells follow the classical tumor evolution from precancerous to a cancerous development, they did not prove the very early step of tumor initiation, which is the transformation of the fallopian tube stem cell.…”

Section: Discussionmentioning

confidence: 99%

Human fallopian tube epithelial cells exhibit stemness features, self-renewal capacity, and Wnt-related organoid formation

2020

Self Cite

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Background: Fallopian tube epithelial cells (FTEC) were thought to be the origin of high-grade serous ovarian carcinoma (HGSOC). Knowledge of the stemness or initiating characteristics of FTEC is insufficient. Previously, we have characterized the stemness cell marker of FTEC, this study aims to further characterize the clonogenicity and spheroid features of FTEC. Methods: We successfully derived FTECs from the epithelial layer of the human fallopian tubes. We examined the morphology, proliferation rate, doubling time, and clonal growth of them. At passage 3, the sphere formations on gelatin-coated culture, suspension culture, and matrigel culture were observed, and the expression of LGR5, SSEA3, SSEA4, and other stemness markers was examined. Furthermore, tissue-reconstituted organoids from coculture of FTEC, fallopian stromal cells (FTMSC) and endothelial cells (HUVEC) were examined.Results: FTEC exhibited cuboidal cell morphology and maintained at a constant proliferation rate for up to nine passages (P9). FTEC could proliferate from a single cell with a clonogenic efficiency of 4%. Flow cytometry revealed expressions of normal stem cell markers (SSEA3, SSEA4, and LGR5) and cancer stem cell markers (CD24, CD44, CD117, ROR1, and CD133). FTEC formed spheres and colonies when cultured on low attach dish. In the presence of Matrigel, the stemness and colony formation activity were much enhanced. In co-culturing with FTMSC and HUVEC, FTEC could form organoids that could be blocked by Wnt inhibitor DKK1. Expressions of LGR5 and FOXJ1 expression were also decreased by adding DKK1. Conclusion: We demonstrated abundantly presence of stem cells in human FTECs which are efficient in forming colonies, spheres and organoids, relying on Wnt signaling. We also reported for the first time the generation of organoid from reconstitutied cell lineages in the tissue. This may provide a new model for studying the regneration and malignant transformation of the tubal epithelium.

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“…These observations, together with the tubal origin of most HGSCs, are shifting the focus to how OCPs affect the biology of the FTE, either directly (through their action on estrogen and progesterone receptors in the tubal epithelium and stroma) or indirectly (by preventing ovulation and thereby exposure of fimbrial epithelium to potentially toxic and pro-inflammatory follicular fluid 40, 41 and blood from the ruptured follicle or retrograde menstrual fluid. 42 …”

Section: Primary Prevention Strategiesmentioning

confidence: 99%

“…44 The protective effect afforded by tubal ligation on HGSC could also be a result of decreased blood flow to or atrophy of the distal end of the fallopian tube or by decreased exposure of the fimbrial epithelium to blood in retrograde menstrual fluid. 42 …”

Section: Primary Prevention Strategiesmentioning

confidence: 99%

Preclinical Models of Ovarian Cancer: Pathogenesis, Problems, and Implications for Prevention

Karnezis

Cho

2017

Clinical Obstetrics &Amp; Gynecology

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Preclinical models are relatively underutilized and underfunded resources for modeling the pathogenesis and prevention of ovarian cancers.1 Several reviews have detailed the numerous published models of ovarian cancer.2–6 In this review, we will provide an overview of experimental model systems, their strengths and limitations, and use selected models to illustrate how they can be used to address specific issues about ovarian cancer pathogenesis. We will then highlight some of the preclinical prevention studies performed to date and discuss experiments needed to address important unanswered questions about ovarian cancer prevention strategies.

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Haemoglobin in pelvic fluid rescues Fallopian tube epithelial cells from reactive oxygen species stress and apoptosis

Abstract: Fallopian tube fimbrial epithelium is considered to be the major site of origin of ovarian high-grade serous carcinoma, with p53 loss being the earliest and universal change. We previously reported that reactive oxygen species (

Cited by 32 publications

References 32 publications

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

Human fallopian tube epithelial cells exhibit stemness features, self-renewal capacity, and Wnt-related organoid formation

Preclinical Models of Ovarian Cancer: Pathogenesis, Problems, and Implications for Prevention

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