Cell of Origin: Exploring an Alternative Contributor to Ovarian Cancer

2013 ◽  
Author(s):  
Bo R. Rueda
Keyword(s):  
Ovarian Cancer ◽  
Cell Of Origin

scholarly journals Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

2013 ◽  
Vol 133 (3) ◽  
pp. 730-739 ◽  
Author(s):  
Joanne Kotsopoulos ◽  
Kathryn L. Terry ◽  
Elizabeth M. Poole ◽  
Bernard Rosner ◽  
Megan A. Murphy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Ovarian Cancer Risk ◽  
Cell Of Origin ◽  
Cancer Risk Factors

Abstract A126: Risk factors for epithelial ovarian cancer by tumor dominance, a surrogate for cell of origin

2010 ◽  
Author(s):  
Joanne Kotsopoulos ◽  
Margaret A. Gates ◽  
Jonathan L. Hecht ◽  
Bernard A. Rosner ◽  
Christopher C. Crum ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Of Origin

Abstract A107: Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

2011 ◽  
Author(s):  
Kathryn L. Terry ◽  
Megan Murphy ◽  
Susan E. Hankinson ◽  
Christopher P. Crum ◽  
Daniel W. Cramer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Ovarian Cancer Risk ◽  
Cell Of Origin ◽  
Cancer Risk Factors

Ovarian cancer in the proteomics era

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 1-6 ◽  
Author(s):  
C. M. Annunziata ◽  
N. Azad ◽  
A. S. Dhamoon ◽  
G. Whiteley ◽  
E. C. Kohn
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
New Technologies ◽  
Molecular Signaling ◽  
Cell Of Origin ◽  
Proteomic Profiling ◽  
Diagnostic Challenge ◽  
High Throughput Analysis ◽  
Tissue Samples ◽  
Protein Array Analysis

Ovarian cancer presents a diagnostic challenge because of its subtle clinical presentation and elusive cell of origin. Two new technologies of proteomics have advanced the dissection of the underlying molecular signaling events and the proteomic characterization of ovarian cancer: mass spectrometry and protein array analysis. Mass spectrometry can provide a snapshot of a proteome in time and space, with sensitivity and resolution that may allow identification of the elusive “needle in the haystack” heralding ovarian cancer. Proteomic profiling of tumor tissue samples can survey molecular targets during treatment and quantify changes using reverse phase protein arrays generated from tumor samples captured by microdissection, lysed and spotted in serial dilutions for high-throughput analysis. This approach can be applied to identify the optimal biological dose of a targeted agent and to validate target to outcome link. The evolution of proteomic technologies has the capacity to advance rapidly our understanding of ovarian cancer at a molecular level and thus elucidate new directions for the treatment of this disease

scholarly journals Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

2018 ◽  
Author(s):  
Kate Lawrenson ◽  
Marcos A.S. Fonseca ◽  
Felipe Segato ◽  
Janet M. Lee ◽  
Rosario I. Corona ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Tumor Development ◽  
Molecular Profiling ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Ovarian Cancers ◽  
Integrative Analyses ◽  
Ovarian Surface Epithelial

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.

scholarly journals UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 262 ◽  
Author(s):  
Laura Hardy ◽  
Amrita Salvi ◽  
Joanna Burdette
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Cancer Progression ◽  
Drug Targets ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Pax8 Expression

High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

scholarly journals Characteristics of in Vivo Model Systems for Ovarian Cancer Studies

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 120 ◽  
Author(s):  
Tudrej ◽  
Kujawa ◽  
Cortez ◽  
Lisowska
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Xenograft Model ◽  
Cellular Migration ◽  
Model Systems ◽  
In Vivo Model ◽  
Preclinical Studies ◽  
Cell Of Origin ◽  
Mice Model ◽  
Mesenchymal Transition

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.

scholarly journals New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact

2008 ◽  
Vol 26 (32) ◽  
pp. 5284-5293 ◽  
Author(s):  
Keren Levanon ◽  
Christopher Crum ◽  
Ronny Drapkin
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Genetic Alterations ◽  
Model Systems ◽  
Evolutionary Stage ◽  
High Grade ◽  
Cell Of Origin ◽  
Neoplastic Tissue ◽  
Cancer Pathogenesis ◽  
Binary Model

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.

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