Comparative evaluation of cancer stem cell markers in normal pancreas and pancreatic ductal adenocarcinoma

Vizio, Barbara; Mauri, Francesco; Prati, Adriana; Trivedi, Pritesh; Giacobino, Alice; Novarino, Anna; Satolli, Maria Antonietta; Ciuffreda, Libero; Camandona, Michele; Gasparri, Guido; Bellone, Graziella

doi:10.3892/or.2011.1461

Cited by 15 publications

(15 citation statements)

References 54 publications

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“…The presence of SP fraction in PANC-1, SW1990, and BxPc-3 cells and the CSC-like properties of these SP cells have been documented by other groups [7–14,23]. We provided both in vitro and in vivo evidence for the ability of the SP cells from h-PCCLs to regenerate a population of cells comprised of both SP and NSP, indicating the self-renewal ability to produce heterologous descendent cells by asymmetric division.…”

Section: Discussionsupporting

confidence: 71%

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells

et al. 2013

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BackgroundA major challenge in the treatment of pancreatic ductal adenocarcinoma is the failure of chemotherapy, which is likely due to the presence of the cancer stem cells (CSCs).ObjectiveTo identify side population (SP) cells and characterize s-like properties in human pancreatic cancer cell lines (h-PCCLs) and to exploit the efficacy of concomitant targeting of multiple key transcription factors governing the stemness of pancreatic CSCs in suppressing CSC-like phenotypes.MethodsFlow cytometry and Hoechst 33342 DNA-binding dye efflux assay were used to sort SP and non-SP (NSP) cells from three h-PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness, migration and drug resistance of SP cells were evaluated. Expression of CSC marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO) designed to simultaneously targeting Sox2, Oct4 and c-Myc were assessed.ResultsCSCs were enriched in the side proportion (SP) cells contained in the h-PCCLs and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with NSP cells. SP cells overexpressed stem cell markers CD133 and ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene ABCG2. Moreover, SP cells consistently demonstrated significantly greater tumorigenicity than NSP cells in xenograft model of nude mice. CdODN–SOC efficiently suppressed all CSC properties and phenotypes, and minimized the tumorigenic capability of the SP cells and the resistance to chemotherapy. By comparison, the negative control failed to do so.ConclusionThe findings indicate that targeting the key genes conferring the stemness of CSCs can efficiently eliminate CSC-like phenotypes, and thus may be considered a new approach for cancer therapy. Specifically, the present study establishes the combination of Sox2/Oct4/c-Myc targeting as a potential anti-pancreatic cancer agent worthy of further studies in preclinical settings.

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Section: Discussionsupporting

confidence: 71%

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells

et al. 2013

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“…This confirms similar results obtained by Hermann et al , who also showed that CD133+ pancreatic cancer cells were resistant to very high concentrations of gemcitabine (100 µg/ml) [23]. Very recently, expression of CD133 has been correlated with increased migration and invasion by epithelial to mesenchymal transition (EMT) [58]. The EMT potential of JoPaca-1 is currently under investigation.…”

Section: Discussionsupporting

confidence: 88%

Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System

et al. 2012

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Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence of tumours. Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumours that were histologically very similar to the primary tumour. The high heterogeneity of JoPaca-1 was reflected by diverse cell morphology and a substantial number of chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC-3 revealed mutations in genes frequently altered in pancreatic cancer. Exceptionally high expression of cancer stem cell markers and a high clonogenic potential in vitro and in vivo was observed. All of these attributes make this cell line an extremely valuable model to study the biology of and pharmaceutical effects on pancreatic cancer.

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“…The authors showed that the immunoactivity of CD133 did not differ between both groups of analyzed patients. Furthermore, CD133 expression did not correlate with tumor stage [30]. Interestingly, similar results were shown in murine model of PDAC.…”

Section: Discussionmentioning

confidence: 70%

Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis

et al. 2017

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Cancer stem cells (CSC) play an important role in pancreatic carcinogenesis and prognosis. The study aimed at examining the expression of CD24, CD44, and CD133 in human PDAC and CP in order to evaluate its clinicopathological correlations and the clinical significance. Surgical specimens from 23 patients with PDAC and 15 patients with chronic pancreatitis after pancreatic resection were stained with CD24, CD44, and CD133 antibodies. The intensity of staining was scored from 0 (negative) to 3 (strongly positive). Results. Mean CD24 staining score in PDAC was 1.38 ± 0.76 and was significantly higher than that in CP: 0.70 ± 0.53 (p < 0.01); CD44 score in PDAC was 2.23 ± 0.42 and was significantly higher than that in CP: 1.87 ± 0.55 (p < 0.05); CD133 score 0.93 ± 0.58 was not different from CP: 0.71 ± 0.43 (p > 0.05). CD44 immunoreactivity was significantly higher (p < 0.05) in pT1 and pT2 patients together as regards pT3: 2.45 ± 0.37 versus 2.06 ± 0.38 as well as in N0 patients compared to N1 patients: 2.5 ± 0.38 versus 2.04 ± 0.34. Conclusions. CD24 and CD44 are upregulated in human pancreatic cancer compared to chronic pancreatitis. CD44 immunoreactivity decreases with the tumor advancement and may represent the negative PDAC prognostic factor. Each CSC marker was differently related to PDAC advancement. CD133 may lack clinical significance in PDAC.

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Comparative evaluation of cancer stem cell markers in normal pancreas and pancreatic ductal adenocarcinoma

Cited by 15 publications

References 54 publications

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells

Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System

Expression and Clinical Significance of Cancer Stem Cell Markers CD24, CD44, and CD133 in Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis

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