KRAS mutation associated with CD44/CD166 immunoexpression as predictors of worse outcome in metastatic colon cancer

Ribeiro, Karen Bento; Zanetti, Juliana da Silva; Ribeiro‐Silva, Alfredo; Rapatoni, Liane; Oliveira, Harley Francisco de; Tirapelli, Daniela Pretti da Cunha; Garcia, Sérgio Britto; Féres, Omar; Rocha, José Joaquim Ribeiro da; Peria, Fernanda Maris

doi:10.3233/cbm-160592

Cited by 26 publications

(29 citation statements)

References 38 publications

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“…CSCs are identified by specific surface epitopes. In CRC, CD133, CD24, CD44, CD166, EpCAM, and ALDHA1 are reported as CSC markers [15–18]. Cells expressing these surface epitopes have the ability to form tumors at a much diluted concentration in SCID mice that histologically resemble the primary tumor from which they were derived [19].…”

Section: Introductionmentioning

confidence: 99%

“…Several stages of carcinogenesis in colon cancer comprise subpopulations of CSCs, which are responsible for tumor cell transformation, growth, and proliferation. Recently, it has been reported that the expression CSC markers CD44 and CD166, associated with KRAS mutation in primary colonic tumors, represent a higher risk of lymph node involvement by the tumor and development of liver and lung metastasis [18]. …”

Section: Introductionmentioning

confidence: 99%

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Bile acid: a potential inducer of colon cancer stem cells

Farhana

Nangia‐Makker

Arbit³

et al. 2016

Stem Cell Res Ther

136

100

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BackgroundAlthough the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer.MethodsNormal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs. The expression of CSC markers was measured by real-time qPCR. Flow cytometry was used to isolate CSCs. T-cell factor/lymphoid-enhancing factor (TCF/LEF) luciferase assay was employed to examine the transcriptional activity of β-catenin. Downregulation of muscarinic 3 receptor (M3R) was achieved through transfection of corresponding siRNA.ResultsWe found DCA/LCA to induce CSCs in normal human colonic epithelial cells, as evidenced by the increased proportion of CSCs, elevated levels of several CSC markers, as well as a number of epithelial–mesenchymal transition markers together with increased colonosphere formation, drug exclusion, ABCB1 and ABCG2 expression, and induction of M3R, p-EGFR, matrix metallopeptidases, and c-Myc. Inhibition of M3R signaling greatly suppressed DCA/LCA induction of the CSC marker ALDHA1 and also c-Myc mRNA expression as well as transcriptional activation of TCF/LEF.ConclusionsOur results suggest that bile acids, specifically DCA and LCA, induce cancer stemness in colonic epithelial cells by modulating M3R and Wnt/β-catenin signaling and thus could be considered promoters of colon cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bile acid: a potential inducer of colon cancer stem cells

Farhana

Nangia‐Makker

Arbit³

et al. 2016

Stem Cell Res Ther

136

100

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“…CD44 is a type 1, 85-200 kDa transmembrane glycoprotein expressed in both normal and tumor tissues [16,27,28]. Discovered initially as a receptor for hyaluronic acid, the molecule has retained its affinity for it and for other components like collagens, osteopontin, or type I metalloproteinase [3,27]. Supplementary, an adhesion function was highlighted for CD44 that was found to intervene in both cell-cell and cell-matrix interactions [4,16].…”

Section: Cd44 In Colon Cancermentioning

confidence: 99%

“…Colon cancer stem cells (CCSCs) are multipotent neoplastic cells that have the ability to differentiate and initiate the carcinogenesis process [3]. Due to their increased viability, CCSCs are responsible for both tumor growth and tumor recurrence [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Detection of cancer stem cells (CSCs) in various digestive and extra-digestive cancers has been a topic of great interest in the literature of recent years and was frequently done using cluster of differentiation (CD) markers. In colon cancer, various biomarkers have been identified at the surface of CSCs, and their role in colon cancer is currently being tested: EpCAM, CD133, CD29, CD24, CD44, CD166, ALDH1A1, and ALDH1B1 [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Stem Cell Markers in Colon Cancer

Pop¹

2019

Basic Principles and Practice in Surgery

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Colon cancer incidence is increasing in young people. Even if, so far, colon cancer had a maximum incidence in the sixth and seventh decades of life, lately its incidence in people age 50 and younger is increasing. Thus, colon cancer still represents a major health problem despite constant research made in the field. Early detection of colon cancer is mandatory for an appropriate treatment of the disease and to attain increased overall survival. Even if various stem cell markers have been studied in order to evaluate their prognostic value in colon cancer cases, results in literature are heterogeneous, and no clear consensus has been drafted so far. This paper aims to review the most important stem cell markers identified in colon cancer and to establish their role in both cancer diagnosis and progression.

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Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors

Tolba

2020

Intl Journal of Cancer

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Colorectal cancer (CRC) represents the third cause of cancer-related mortalities worldwide. The progression of CRC to the metastatic phase significantly compromises the overall survival rates. Despite the advances in the therapeutic protocols, CRC treatment is still challenging. Cancer immunotherapy joined the ranks of surgery, chemotherapy, radiotherapy and targeted therapy as the fifth pillar in the foundation of cancer therapeutics. Interruption of the immunosuppressive signals within the tumor microenvironment and reactivation of antitumor immunity via targeting the molecular immune checkpoints generated promising therapeutic outcomes in several types of hard-to-treat cancers. The year 2017 witnessed the first US Food and Drug Administration (FDA) approval of immune checkpoint inhibitor (ICI) immunotherapy for the management of CRC. The approval was granted to pembrolizumab (anti-PD-1) for the treatment of patients with advanced/metastatic solid malignancies with mismatch-repair deficiency including CRCs. Such natively immunogenic tumors constitute only a minor percentage of all CRCs. Therefore, it is imperative to utilize novel combinatorial regimens to enhance the response of a wider range of CRC tumors to cancer immunotherapy and help in extending the survival rates in patients with advanced/metastatic disease. This review highlights the novel approaches under clinical development to overcome the resistance of CRCs to immunotherapy and improve the therapeutic outcomes. K E Y W O R D S clinical trials, colon cancer, immune checkpoint inhibitors, immunotherapy 1 | INTRODUCTION Colorectal cancer (CRC) is ranked as the third cause of cancer death worldwide. 1 The progression to the metastatic stage cuts down the overall survival rate to 10%. 2 Advances in treatment options for the metastatic stage of the disease only extended the median overall survival from 18 to 30 months. 2,3 Therefore, it is imperative to find better therapeutic strategies for patients with advanced/metastatic CRC. Cancer Immunotherapy is considered the fifth pillar for cancer therapy that proved effectiveness in the management of several types of hard-to-treat cancers. 4,5 Clinical testing of programmed cell death receptor (PD)-1 mAb in patients with metastatic CRC demonstrated promising outcomes with progression-free survival rates of 78% and 11% in mismatch-repair-deficient (dMMR) vs mismatch-repairproficient (pMMR) tumors. 6,7 It is noteworthy that dMMR or microsatellite unstable (MSI) CRC tumors represent only a small percentage

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KRAS mutation associated with CD44/CD166 immunoexpression as predictors of worse outcome in metastatic colon cancer

Cited by 26 publications

References 38 publications

Bile acid: a potential inducer of colon cancer stem cells

Bile acid: a potential inducer of colon cancer stem cells

Stem Cell Markers in Colon Cancer

Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors

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