Oncotarget

Research Papers:

Temporal and spatial changes of cells positive for stem-like markers in different compartments and stages of human colorectal adenoma-carcinoma sequence

Guanglin Cui _, Gang Xu, Li Zhu, Zhigang Pang, Wei Zheng, Zhenfeng Li and Aping Yuan

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Oncotarget. 2017; 8:45311-45322. https://doi.org/10.18632/oncotarget.17330

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Abstract

Guanglin Cui1,2, Gang Xu1, Li Zhu1, Zhigang Pang1, Wei Zheng1, Zhenfeng Li1, Aping Yuan1

1Research Group of Gastrointestinal Diseases, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

2Faculty of Health, Nord University, Levanger, Norway

Correspondence to:

Guanglin Cui, email: [email protected]

Keywords: stem-like marker, tumorigenesis, colorectum

Received: October 13, 2016     Accepted: April 11, 2017     Published: April 21, 2017

ABSTRACT

Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma. Notably, the population of cells positive for stem-liker markers was expanded from the base to the middle part of the transitional crypt in both adenoma and CRC tissues, reflecting that stem-like cells are likely involved in the process of colorectal tumorigenesis. Counting results showed that the grading scores of cells positive for LGR5 and ALDH1 in the adenoma/CRC epithelium were significantly increased relative with the control epithelium, and associated with the degree of dysplasia in the adenoma and node involvement in the CRC (all P < 0.05). In addition, the density of cells positive for stem–like markers in the adenomatous/cancerous stroma was also increased and paralleled an increase in the density of proliferative stromal cells labeled by PCNA, which were primarily identified as vimentin positive fibroblasts. Our results have revealed a changed temporal and spatial presentation of stem-like markers in different stages of human colorectal adenoma-carcinoma sequence, which might be a hallmark of the adenoma-carcinoma transition.


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