The CD133 expression levels and its role as potential cancer stem cells marker in gastrointestinal stromal tumor

Bozzi, Fabio; Tamborini, Elena; Pilotti, Silvana

doi:10.1002/ijc.27374

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Three common clinical features of primary GIST are used for risk assessment: size, mitotic index, and location; however, a subset of GIST patients classified as low-risk have metastasis (36). Several recent studies have aimed to identify prognostic biomarkers for GIST and have reported that high prominin 1 (PROM1) expression in tissue is associated with poor prognosis (137)(138)(139). In this study, we report for the first time, that the proteome of GIST-derived exosomes consists of prognostic markers of GIST, included CDKN2A, EPHA4, FHL2, DPP4, EZR (140), HIF1A (117,120), and KCTD12 (also known as Pfetin) (141,142).…”

Section: Discussionmentioning

confidence: 99%

Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers

Atay

Wilkey

Milhem³

et al. 2018

Molecular & Cellular Proteomics

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Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity. In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT. Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules. To this aim, we performed the first high quality proteomic study of GISTderived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp). The cGDEp was enriched in diagnostic markers (e.g. KIT, CD34, ANO1, PROM1, PRKCQ, and ENG), as well as proteins encoded by genes previously reported expressed in GIST (e.g. DPP4, FHL1, CDH11, and KCTD12). Many of these proteins were validated using cell lines, patient-derived KIT ؉ exosomes, and GIST tissues. We further show that in vitro and in vivo-derived GDE, carry proteins associated with IM response, such as Sprouty homolog 4 (SPRY4), surfeit 4 (SURF4), ALIX, and the cGMP-dependent 3,5cyclic phosphodiesterase 2A (PDE2A). Additionally, we report that the total exosome levels and exosome-associated KIT and SPRY4 protein levels have therapeutic values. In fact, molecular characterization of in vivo-derived KIT ؉ exosomes indicate significant sorting of p-KIT Tyr719 , total KIT, and SPRY4 after IM-treatment of metastatic patients as compared with the pre-IM levels. Our data suggest that analysis of circulating exosomes levels

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Section: Discussionmentioning

confidence: 99%

Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers

Atay

Wilkey

Milhem³

et al. 2018

Molecular & Cellular Proteomics

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“… 3 CSC occurrence have been confirmed in several tumour types, including gastric cancer stem cells (GCSCs). 4 , 5 , 6 , 7 GCSCs can be characterized by several biomarkers, such as CD44, 7 Lgr5, 8 CD133 9 and CD90. 10 Furthermore, GCSCs have been considered a relevant subset of targets for an efficient GC treatment.…”

Section: Introductionmentioning

confidence: 99%

The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells

Wang

Sun

Zhu

et al. 2021

J Cellular Molecular Medi

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A combination of valproic acid sodium salt, CHIR99021, E-616452, tranylcypromine, and 3-Deazaneplanocin A causes stem cell-like characteristics in cancer cells

et al. 2017

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Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1. The A549 stem-like cells displayed resistance to the chemotherapeutic drugs etoposide and cisplatin, epithelial-to-mesenchymal transition properties, and increased protein expression levels of NOTCH1 and Hes Family bHLH Transcription Factor 1 (HES1). When A549 cells were pretreated with a NOTCH signaling pathway inhibitor before compound induction, expression of the NOTCH1 target gene HES1 was reduced. This demonstrated that the NOTCH signaling pathway in the putative A549 stem-like cells had been activated. Together, the results of our study showed that a combination of five small molecule agents could transform A549 cells into putative stem-like cells, and that these compounds could also elevate CD133 and ABCG2 protein expression levels in H460 cells. This study provides a convenient method for obtaining lung CSLCs, which may be an effective strategy for developing lung carcinoma treatments.

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The CD133 expression levels and its role as potential cancer stem cells marker in gastrointestinal stromal tumor

Cited by 3 publications

References 10 publications

Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers

Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers

The stabilization of yes‐associated protein by TGFβ‐activated kinase 1 regulates the self‐renewal and oncogenesis of gastric cancer stem cells

A combination of valproic acid sodium salt, CHIR99021, E-616452, tranylcypromine, and 3-Deazaneplanocin A causes stem cell-like characteristics in cancer cells

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