Co-expression of Lgr5 and CXCR4 characterizes cancer stem-like cells of colorectal cancer

Wu, Weidong; Cao, Jun; Ji, Zhengyi; Wang, Jingjue; Jiang, Tao; Ding, Haiyan

doi:10.18632/oncotarget.13214

Cited by 36 publications

(29 citation statements)

References 48 publications

(41 reference statements)

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“…We have also found that grading scores of LGR5 and ALDH1 positive cells in the cancerous epithelium were significantly increased in CRC patients with advanced TNM stages than those with early stages. Those observations are consist with other groups’ findings [ 15 , 26 – 32 ], and imply that increased stem-like cell density might be the potential predicators for disease stage progression in both the adenoma and CRC. Mesenchymal stem like cell can be observed in the tumor stroma, it plays a critical role in remodeling tumor stroma and forming a supportive environment for cancer growth and metastasis [ 33 ].…”

Section: Discussionsupporting

confidence: 90%

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

Cui

Zhu

et al. 2017

Oncotarget

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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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Section: Discussionsupporting

confidence: 90%

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

Cui

Zhu

et al. 2017

Oncotarget

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“…Lgr-5 plays an active role in pathogenesis of colorectal cancer [ 43 ], and the Lgr5 expression is closely related to tumorigenesis, 5-fluorouracil resistance and recurrence of colorectal cancer [ 43 , 44 ]. In stage IV colorectal cancer, high Lgr5 expression is associated with poor prognosis [ 45 ]. Therefore, Lgr5 is considered an indicator of poor prognosis and a potential target of colorectal cancer.…”

Section: Colorectal Cancer Stem Cellsmentioning

confidence: 99%

Cancer stem cells in progression of colorectal cancer

et al. 2017

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Colorectal cancer is one of the most common cancers worldwide with high mortality. Distant metastasis and relapse are major causes of patient death. Cancer stem cells (CSCs) play a critical role in the metastasis and relapse of colorectal cancer. CSCs are a subpopulation of cancer cells with unique properties of self-renewal, infinite division and multi-directional differentiation potential. Colorectal CSCs are defined with a group of cell surface markers, such as CD44, CD133, CD24, EpCAM, LGR5 and ALDH. They are highly tumorigenic, chemoresistant and radioresistant and thus are critical in the metastasis and recurrence of colorectal cancer and disease-free survival. This review article updates the colorectal CSCs with a focus on their role in tumor initiation, progression, drug resistance and tumor relapse.

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“…It is a downstream target gene of the Wnt/β-catenin signaling pathway and plays an important role in the embryonic development and organogenesis [ 1 , 2 ]. Recently, some studies show that Lgr5 is a marker of stem cells in small intestine and colon [ 3 ] and cancer stem-like cells of colorectal carcinoma (CRC) [ 4 ], and its over-expression is also detectable in CRC. Although R-spondin has been confirmed as a ligand of Lgr5 [ 5 ], the intracellular signaling pathway related to Lgr5 is still unclear, and the correlation of Lgr5 with the occurrence, maintenance and metastasis of CRC is also poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous expression of Lgr5 as a risk factor for focal invasion and distant metastasis of colorectal carcinoma

Zheng

Huang

et al. 2018

Oncotarget

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Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a downstream target gene of the Wnt/β-catenin signaling pathway and identified as a marker of cancer stem-like cells of colorectal carcinoma (CRC). Here, the heterogeneous expression pattern of Lgr5 and its clinical significance were studied by the method of immunohistochemistry in 204 CRC tumors at various pTNM stages. Lgr5 expression was found in 82.4% (168/204) cases, significantly more common in neoplastic cells at the infiltrative front (n = 59.5%, 110/185) or at the expanding front (n = 36.4%, 59/162) than at the tumor center (n = 16.7%, 34/204; P < 0.01). Tumor budding (TB) was discovered with significantly higher Lgr5 expression (n = 39.3%, 57/145, P = 0.03) and significantly positively correlated between Lgr5 expression and TB grade (r = 0.19, P = 0.02). Additionally, both positive Lgr5 expression and a high TB grade were significantly correlated to the depth of tumor invasion, lymph node metastasis, pTNM stage, and perineural invasion (P < 0.01). The study results suggest that heterogeneous expression of Lgr5 may be a risk factor for local invasion and distant metastasis of CRC.

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Co-expression of Lgr5 and CXCR4 characterizes cancer stem-like cells of colorectal cancer

Cited by 36 publications

References 48 publications

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

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

Cancer stem cells in progression of colorectal cancer

Heterogeneous expression of Lgr5 as a risk factor for focal invasion and distant metastasis of colorectal carcinoma

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