Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic changes in precursor lesions of serous papillary carcinoma
K Bahar-Shany, H Brand, S Sapoznik… - Gynecologic …, 2014 - Elsevier
K Bahar-Shany, H Brand, S Sapoznik, J Jacob-Hirsch, Y Yung, J Korach, T Perri, Y Cohen…
Gynecologic oncology, 2014•ElsevierObjectives Ovulation-related inflammation is suspected to have a causal role in ovarian
carcinogenesis, but there are no human models to study the molecular pathways. Our aim is
to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed
to human follicular fluid (FF). Methods FT epithelium was dissociated from normal surgical
specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were
cultured on collagen-coated Transwells and incubated with FF for various periods of time …
carcinogenesis, but there are no human models to study the molecular pathways. Our aim is
to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed
to human follicular fluid (FF). Methods FT epithelium was dissociated from normal surgical
specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were
cultured on collagen-coated Transwells and incubated with FF for various periods of time …
Objectives
Ovulation-related inflammation is suspected to have a causal role in ovarian carcinogenesis, but there are no human models to study the molecular pathways. Our aim is to develop such an ex-vivo model based on human fallopian tube (FT) epithelium exposed to human follicular fluid (FF).
Methods
FT epithelium was dissociated from normal surgical specimens. FF was obtained from donors undergoing in-vitro fertilization. The cells were cultured on collagen-coated Transwells and incubated with FF for various periods of time. The transcriptomic changes resulting from FF treatment were profiled using Affymetrix expression arrays. Specific characteristics of the FT pre-cancerous lesions were studied using immunohistochemistry, immunofluorescence, RT-PCR and XTT assay.
Results
We show that FF exposure causes up-regulation of inflammatory and DNA repair pathways. Double stranded DNA breaks are induced. There is a minor increase in cell proliferation. TP53, which is the hallmark of the precursor lesion in-vivo, is accumulated. Levels of expression and secretion of Interleukin-8 are significantly increased.
Conclusions
Our model addresses the main non-genetic risk factor for ovarian cancer, namely the impact of ovulation. This study demonstrates the biological implications of in-vitro exposure of human FT epithelial cells to FF. The model replicates elements characterizing the precursor lesions of ovarian cancer, and warrants further investigation of the linkage between repeated exposure to ovulation-related damage and accumulation of neoplastic changes.
Elsevier