Tumour-initiating cells vs. cancer ‘stem’ cells and CD133: What’s in the name?

Neužil, Jiřı́; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Procházka, Lubomír; Dong, Lan-Feng; Anděra, Ladislav; Ralph, Stephen John

doi:10.1016/j.bbrc.2007.01.159

Cited by 173 publications

(128 citation statements)

References 50 publications

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“…Recently, signatures of these CIC have been identified for several tumor types (35) and CD44 is one of these CIC markers shared by different tumor types including pancreatic adenocarcinoma (36), which emphasizes its role in metastasis promotion. However, little is known about pathways, whereby these CIC markers contribute to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Klingbeil

Marhaba

Jung

et al. 2009

Molecular Cancer Research

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CD44 designates a large family of proteins with a considerable structural and functional diversity, which are generated from one gene by alternative splicing. As such, the overexpression of CD44 variant isoform (CD44v) has been causally related to the metastatic spread of cancer cells. To study the underlying mechanism, stable knockdown clones with deletion of exon v7 containing CD44 isoforms (CD44v kd ) of the highly metastatic rat adenocarcinoma line BSp73ASML (ASML wt ) were established. ASML-CD44v kd clones hardly form lung metastases after intrafootpad application and the metastatic load in lymph nodes is significantly reduced. Rescuing, albeit at a reduced level, CD44v expression in ASML-CD44v kd cells (ASML-CD44v rsc ) restores the metastatic potential. The following major differences in ASML wt , ASML-CD44v kd , and ASML-CD44v rsc clones were observed: (a) ASML wt cells produce and assemble a matrix in a CD44v-dependent manner, which supports integrin-mediated adhesion and favors survival. This feature is lost in the ASML-CD44v kd cells. (b) CD44v cross-linking initiates phosphatidylinositol 3-kinase/Akt activation in ASML wt cells. Accordingly, apoptosis resistance is strikingly reduced in ASML-CD44v kd cells. The capacity to generate an adhesive matrix but not apoptosis resistance is restored in ASML-CD44v rsc cells. These data argue for a 2-fold effect of CD44v on metastasis formation: CD44v-mediated matrix formation is crucial for the settlement and growth at a secondary site, whereas apoptosis resistance supports the efficacy of metastasis formation.

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Section: Discussionmentioning

confidence: 99%

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Klingbeil

Marhaba

Jung

et al. 2009

Molecular Cancer Research

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“…Other key features include activation of pluripotency genes (Oct4, Sox2, Nanog), formation of tumor spheres in low-adherence cultures, and multi-drug resistance. CSCs can be identifi ed by distinct markers, including the cell surface marker CD133 (also known as prominin 1), BMI1 and CD44 (Neuzil et al, 2007) [ Figure 1 and Wang et al, 2012a). There is increasing evidence that connects the SHH/GLI pathway and tumor initiation specific markers as targets (Katoh and Katoh, 2009).…”

Section: Initiationmentioning

confidence: 99%

Sonic Hedgehog in cancer stem cells: a novel link with autophagy

2012

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The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefl y discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.

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“…Since then, recent evidence suggests that a subset of cells within a tumour has stem-like characteristics, including the ability to initiate tumours, high proliferative rates, a high capacity of self-renewal, and the propensity to differentiate into actively proliferating tumour cells (Reya et al, 2001;Presnell et al, 2002;Pardal et al, 2003). These stem-like tumour cells are often associated with elevated expression of the stem cell surface marker CD133 (Neuzil et al, 2007).…”

mentioning

confidence: 99%

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

et al. 2008

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Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P ¼ 0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P ¼ 0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P ¼ 0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P ¼ 0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.

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Tumour-initiating cells vs. cancer ‘stem’ cells and CD133: What’s in the name?

Cited by 173 publications

References 50 publications

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Sonic Hedgehog in cancer stem cells: a novel link with autophagy

CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer

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