Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube.

Masahiko Kito,Yukihiro Terada,Tian-Li Wang,Yukitsugu Kudo-Asabe,Ie-Ming Shih,Naoki Sato,Akiteru Goto,Masamitsu Tanaka,Daichi Maeda,Hiroyoshi Ariga

doi:10.1371/journal.pone.0156069

Masahiko Kito, Yukihiro Terada + Show 8 more

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https://doi.org/10.1371/journal.pone.0156069

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Journal: PloS one	Publication Date: Jun 3, 2016
Citations: 1	License type: CC BY 4.0

Affiliation: Akita University, Johns Hopkins University

Abstract

There is a growing body of evidence regarding cell competition between normal and mutant mammalian cells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412 – 1.211 for p53 signature and 0.9790 (95% CI, 0.7206 – 1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations.

Highlights

To examine the expression of cell competition markers at the interface between normal and transformed epithelial cells, we focused on studying the p53 signature of the human fallopian tube, a putative precursor of pelvic high-grade serous carcinoma.[14,15]
We examined human serous tubal intraepithelial lesion (STIL),another tubal lesion with TP53 altertation which is more advanced than p53 signature in tumor progression
VMN positivity was demonstrated at varying intensities throughout the tubal epithelium, including p53 signatures

Summary

Introduction

Normal and transformed epithelial cells often compete with each other for cell survival, a phenomenon called cell competition.[1,2] Cell competition was initially confirmed in Drosophila in 1975 and has been recently shown in mammalian cells.[3,4,5,6,7] Cell competition is considered a unique type of short-range cell-to-cell communication that may take place during the early stages of carcinogenesis.[7,8] Genes such as myc, scribble, sparc and mahjong have been shown to play an important role in this process.[9,10,11,12,13] Based on the results of in vitro studiesPLOS ONE | DOI:10.1371/journal.pone.0156069 June 3, 2016. Normal and transformed epithelial cells often compete with each other for cell survival, a phenomenon called cell competition.[1,2] Cell competition was initially confirmed in Drosophila in 1975 and has been recently shown in mammalian cells.[3,4,5,6,7] Cell competition is considered a unique type of short-range cell-to-cell communication that may take place during the early stages of carcinogenesis.[7,8] Genes such as myc, scribble, sparc and mahjong have been shown to play an important role in this process.[9,10,11,12,13] Based on the results of in vitro studies.

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