The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

Fujiwara, Daisuke; Kato, Kazunori; Nohara, Shigeo; Iwanuma, Yoshimi; Kajiyama, Yoshiaki

doi:10.1016/j.bbrc.2013.04.008

Cited by 23 publications

(23 citation statements)

References 33 publications

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“…The enhancement of CA IX expression in BTSC was time dependent. Consistent with our findings are those in 3D esophageal squamous carcinoma stem cell lines TE2 and TTn where CA IX in the 7-day old spheroids was significantly increased [53]. The very high and specific expression of CA IX in the BTSC is an interesting finding indicating usefulness of BTSC in drug development for reoccurring GBM.…”

Section: Discussionsupporting

confidence: 79%

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Amiri

Moquin

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tCarbonic anhydrase IX (CA IX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches is the standard treatment but not effective in long term. In this study we tested the treatment with acetazolamide (ATZ), an inhibitor of CA IX, alone or combined with TMZ. The experiments were performed in 2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor stem cells (BTSCs). Several proteins implicated in tumor cell death were also investigated. The key results from these studies suggest the following: (1) Cell death of human glioblastoma spheroids and BTSC is significantly increased with combined treatment after 7 days, and (2) the effectiveness of ATZ is significantly enhanced against BTSC and U251N when incorporated into nano-carriers. Collectively, these results point toward the usefulness of nano-delivery of CA IX inhibitors and their combination with chemotherapeutics for glioblastoma treatment.

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Section: Discussionsupporting

confidence: 79%

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Amiri

Moquin

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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“…CA IX was shown to be involved in this phenomenon in breast and esophageal carcinoma models [51,[87][88][89]. Expression of CA IX correlates with the expression of a stem cell marker CD44 [89,90] and CA IX targeting by inhibition of its catalytic activity results in the inhibition of breast cancer stem cell expansion in hypoxia indicating that pH-regulating function of CA IX is required for the maintenance of stemness [91]. Moreover, up-regulation of CA IX in cancer-associated fibroblasts (CAFs) in response to ROS-mediated stabilization of HIF-1 in normoxia leads to extracellular acidosis and activation of EMT in epithelial cancer cells [92].…”

Section: The Roles Of Ca IX In Cancermentioning

confidence: 98%

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Pastorek

Pastoreková

2015

Seminars in Cancer Biology

272

230

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“…CA IX also reduces cell-cell adhesion, increases migration and invasion of tumor cells (Svastova et al, 2003; Sansone et al, 2009; Svastova et al, 2012) and its expression and distribution correlates with invasive tumor phenotype (Chen et al, 2005; Rajaganeshan et al, 2009; Deschamps et al, 2012);. CA IX also promotes stemness and correlates with higher histological grades and metastatic disease (Sansone et al, 2007a,b; Storci et al, 2008; Chen et al, 2010; Currie et al, 2013; Fujiwara et al, 2013; Lock et al, 2013). CA IX induces pro-inflammatory phenotype and participates in communication between cancer cells and stroma (Sansone et al, 2009; Fiaschi et al, 2013).…”

Section: Ca IX Role In Cancer Biology: Is It All About Ph Regulation?mentioning

confidence: 99%

Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors

et al. 2014

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Acidic tissue microenvironment contributes to tumor progression via multiple effects including the activation of angiogenic factors and proteases, reduced cell-cell adhesion, increased migration and invasion, etc. In addition, intratumoral acidosis can influence the uptake of anticancer drugs and modulate the response of tumors to conventional therapy. Acidification of the tumor microenvironment often develops due to hypoxia-triggered oncogenic metabolism, which leads to the extensive production of lactate, protons, and carbon dioxide. In order to avoid intracellular accumulation of the acidic metabolic products, which is incompatible with the survival and proliferation, tumor cells activate molecular machinery that regulates pH by driving transmembrane inside-out and outside-in ion fluxes. Carbonic anhydrase IX (CA IX) is a hypoxia-induced catalytic component of the bicarbonate import arm of this machinery. Through its catalytic activity, CA IX directly participates in many acidosis-induced features of tumor phenotype as demonstrated by manipulating its expression and/or by in vitro mutagenesis. CA IX can function as a survival factor protecting tumor cells from hypoxia and acidosis, as a pro-migratory factor facilitating cell movement and invasion, as a signaling molecule transducing extracellular signals to intracellular pathways (including major signaling and metabolic cascades) and converting intracellular signals to extracellular effects on adhesion, proteolysis, and other processes. These functional implications of CA IX in cancer are supported by numerous clinical studies demonstrating the association of CA IX with various clinical correlates and markers of aggressive tumor behavior. Although our understanding of the many faces of CA IX is still incomplete, existing knowledge supports the view that CA IX is a biologically and clinically relevant molecule, exploitable in anticancer strategies aimed at targeting adaptive responses to hypoxia and/or acidosis.

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The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

Cited by 23 publications

References 33 publications

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors

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