Distribution of intestinal stem cell markers in colorectal precancerous lesions

Jang, Bo Gun; Kim, Hye Sung; Kim, Kyung Ju; Rhee, Ye-Young; Kim, Woo Ho; Kang, Gyeong Hoon

doi:10.1111/his.12787

Cited by 31 publications

(39 citation statements)

References 30 publications

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“…OLFM4 is generally expressed in the basal crypt cells and is considered as a specific stem cell protein [31–35]. It is involved in cancer development via antiapoptotic action, in cell proliferation, cell adhesion and metastasis [36–38].…”

Section: Discussionmentioning

confidence: 99%

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

Quesada-Calvo¹,

Massot²,

Bertrand

et al. 2017

Clin Proteom

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BackgroundDespite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient’s survival. MethodsWe analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages.ResultsOut of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed different expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues.ConclusionWe highlighted three proteins that require further investigations to better characterise their role in early CRC carcinogenesis and their potential as early CRC markers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9143-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

Quesada-Calvo¹,

Massot²,

Bertrand

et al. 2017

Clin Proteom

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“…Using previously described protocols, RNA in situ hybridizations (ISH) for GREM1 were performed on 10 TMAs with the RNAscope FFPE assay kit (Advanced Cell Diagnostics, Inc., Hayward, CA, USA) [17]. Briefly, 4-μm TMA sections were baked at 60°C for 1 hour.…”

Section: Methodsmentioning

confidence: 99%

GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas

et al. 2017

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Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.

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“…Additional markers for CBC stem cells include Achaete-Scute homologue 2 (Ascl2) 15 , SPARC-related modular calcium-binding 2 (Smoc2) 16 , Prominin 1(Prom1) 17 , Musashi homologure 1 (Msi1) 18 , Olfactomedin 4 (Olfm4) 19 , and EphB2 20 . Of these, subsequent studies found that the expression of Prom1 21 , Msi1 22 , Olfm4 23 , and Ephb2 23 extends to the transit amplifying cells. Markers of +4 stem cell population are Bmi1, Homeodomain-only (Hopx), Leu-rich repeats and immunoglobulin-like domains 1 (Lrig1), and telomerase reverse transcriptase (Tert) 11 .…”

Section: Introductionmentioning

confidence: 99%

“…Most sporadic colorectal cancers in humans also arise from the mutations in the adenomatous polyposis coli ( APC ) gene, and overexpression of stem cell markers has been demonstrated in the sporadic colorectal tumors 23, 26, 27 . However, there is no direct evidence that these stem cells give rise to colitis-associated colorectal cancers, and the expression of ISC markers in CAC has not been thoroughly studied.…”

Section: Introductionmentioning

confidence: 99%

Expression profile of intestinal stem cell markers in colitis-associated carcinogenesis

Kim¹,

Lee²,

Kim³

et al. 2017

Sci Rep

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The intestinal epithelium has two distinct two stem cell populations, namely, crypt base columnar (CBC) cells and +4 cells. Several specific markers have been identified for each stem cell population. In this study, we examined the expression profiles of these markers in colitis-associated carcinogenesis (CAC) to investigate whether they can be used as biomarkers for the early detection of dysplasia. The expression of intestinal stem cell (ISC) markers was measured by real-time polymerase chain reaction during CAC that was induced by azoxymethane and dextran sodium sulfate treatment. CBC stem cell markers increased continuously with tumor development, whereas a +4 cell expression profile was not present. CBC stem cell population was suppressed in the acute colitis and then expanded to repopulate the crypts during the regeneration period. Notably, RNA in situ hybridization revealed that all dysplasia and cancer samples showed increased expression of CBC stem cell markers in more than one-third of the tumor height, whereas regenerative glands had CBC stem cell markers confined to the lower one-third of the crypt. These results suggest that CBC stem cell markers could be a useful tool for the early detection of colitis-induced tumors.

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Distribution of intestinal stem cell markers in colorectal precancerous lesions

Abstract: The expression and distribution profile of ISC markers possibly provides insights into the organization of stem and progenitor-like cells in each type of precancerous lesion of CRC.

Cited by 31 publications

References 30 publications

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages

GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas

Expression profile of intestinal stem cell markers in colitis-associated carcinogenesis

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