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

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.

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

“…These findings were confirmed in another recent study [ 67 ]; in addition, in this study, it was observed that in serrated lesions other stem cell markers, such as EPHB2 and OLFM4, were distributed in a diffuse manner [ 67 ]. In addition to LGR5 + cells, the adenomatous epithelium also displayed an increased proportion of ALDH1-positive cells [ 68 ]. While in the normal colon positive cells, stem-like markers were shown in the base of normal crypts, in the adenomatous epithelium, the cells positive for stem-like markers were expressed as a patchy destruction on the surface of adenomatous crypts [ 68 ].…”

“…In addition to LGR5 + cells, the adenomatous epithelium also displayed an increased proportion of ALDH1-positive cells [ 68 ]. While in the normal colon positive cells, stem-like markers were shown in the base of normal crypts, in the adenomatous epithelium, the cells positive for stem-like markers were expressed as a patchy destruction on the surface of adenomatous crypts [ 68 ].…”

TH9, TH17, and TH22 Cell Subsets and Their Main Cytokine Products in the Pathogenesis of Colorectal Cancer

“…Colorectal cancer (CRC) is one of the leading causes of high cancer-associated mortality worldwide. According to the colorectal adenoma-carcinoma sequence theory, most CRCs develop from pre-existing adenomatous lesions through a multistep process with the accumulation of genetic, molecular and histological changes (1, 2). This process is significantly influenced by host immunity (3–5).…”

Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: Mechanisms and clinical implications

“…We have previously used a various set of cell markers, such as Musashi, CD133, LGR5 and ALDH1, as biomarkers to examine the presentation of SCs in different compartments of adenomas ( 17 ). We found that populations of SCs labeled by diverse markers were increased in the adenoma tissues.…”

“…In addition, a spatial change in SCs in the adenoma was observed: SCs expanded from the base to the middle part of the transitional crypt and final finally reached the surface of the adenoma, reflecting a changed track pathway of SCs during the development of adenomas. Further analysis revealed that increased populations of LGR5 and aldehyde dehydrogenase 1 (ALDH1) labeled SCs in the adenoma were associated with the degree of dysplasia, suggesting the involvement of SCs in the establishment of adenomas ( 17 ).…”