Gene Expression Analysis of PTEN Positive Glioblastoma Stem Cells Identifies DUB3 and Wee1 Modulation in a Cell Differentiation Model

Forte, Stefano; Pagliuca, Alfredo; Maniscalchi, Eugenia Tiziana; Gulino, Rosario; Calabrese, Giovanna; Ricci–Vitiani, Lucia; Pallini, Roberto; Signore, Michele; Parenti, Rosalba; Maria, Ruggero De; Gulisano, Massimo

doi:10.1371/journal.pone.0081432

Cited by 10 publications

(11 citation statements)

References 20 publications

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“…As previously reported, experimental conditions based on culturing freshly dissociated tumor cells in serum-free medium containing EGF and bFGF, allowed the selective growth of cellular clusters resembling tumor spheres (12,17,18,19,21). In the present study, such spheres maintained an undifferentiated state (UPTC), as confirmed by morphological analysis (Fig.…”

Section: Rna-binding Protein Musashi Is Expressed By Uptc Spheres Butsupporting

confidence: 88%

Resistance of papillary thyroid cancer stem cells to chemotherapy

Giuffrida¹,

Adamo²,

Iannolo³

et al. 2016

Oncology Letters

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Abstract. Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies.

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Section: Rna-binding Protein Musashi Is Expressed By Uptc Spheres Butsupporting

confidence: 88%

Resistance of papillary thyroid cancer stem cells to chemotherapy

Giuffrida¹,

Adamo²,

Iannolo³

et al. 2016

Oncology Letters

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“…In a study by Forte et al [ 33 ], SPRY1 was among a number of genes with elevated expression in the undifferentiated glioblastoma-derived neuropsheres as compared to the differentiated glioblastoma-derived primary cultures. An unrelated study Aldaz et al [ 34 ] demonstrated that SPRY1 was over-expressed at the protein level in undifferentiated cells as opposed to cells that had undergone four days of differentiation.…”

Section: Resultsmentioning

confidence: 99%

Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates

Vidak

Jovčevska

Šamec

et al. 2018

IJMS

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Glioblastoma (GB) is the most aggressive brain malignancy. Although some potential glioblastoma biomarkers have already been identified, there is a lack of cell membrane-bound biomarkers capable of distinguishing brain tissue from glioblastoma and/or glioblastoma stem cells (GSC), which are responsible for the rapid post-operative tumor reoccurrence. In order to find new GB/GSC marker candidates that would be cell surface proteins (CSP), we have performed meta-analysis of genome-scale mRNA expression data from three data repositories (GEO, ArrayExpress and GLIOMASdb). The search yielded ten appropriate datasets, and three (GSE4290/GDS1962, GSE23806/GDS3885, and GLIOMASdb) were used for selection of new GB/GSC marker candidates, while the other seven (GSE4412/GDS1975, GSE4412/GDS1976, E-GEOD-52009, E-GEOD-68848, E-GEOD-16011, E-GEOD-4536, and E-GEOD-74571) were used for bioinformatic validation. The selection identified four new CSP-encoding candidate genes—CD276, FREM2, SPRY1, and SLC47A1—and the bioinformatic validation confirmed these findings. A review of the literature revealed that CD276 is not a novel candidate, while SLC47A1 had lower validation test scores than the other new candidates and was therefore not considered for experimental validation. This validation revealed that the expression of FREM2—but not SPRY1—is higher in glioblastoma cell lines when compared to non-malignant astrocytes. In addition, FREM2 gene and protein expression levels are higher in GB stem-like cell lines than in conventional glioblastoma cell lines. FREM2 is thus proposed as a novel GB biomarker and a putative biomarker of glioblastoma stem cells. Both FREM2 and SPRY1 are expressed on the surface of the GB cells, while SPRY1 alone was found overexpressed in the cytosol of non-malignant astrocytes.

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“…Since it is known that PTEN [63] is one of the predicted targets of miR-19a, it is also possible that miR-19a overexpression might be associated with PTEN inactivation inducing cell proliferation in FTC-133, while its inhibition promotes PTEN activation inducing cell growth reduction. In a recent study, Frisk et al have suggested that PTEN suppression is associated in extremely malignant or late-stage thyroid tumors, including ATC [64]. These results suggest that miR-19a leads to the poor prognosis in follicular thyroid cancer cells through stimulating cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

MiR-19a Overexpression in FTC-133 Cell Line Induces a More De-Differentiated and Aggressive Phenotype

Calabrese¹,

Dolcimascolo²,

Torrisi³

et al. 2018

IJMS

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In recent years, microRNAs (miRNAs) have received increasing attention for their important role in tumor initiation and progression. MiRNAs are a class of endogenous small non-coding RNAs that negatively regulate the expression of several oncogenes or tumor suppressor genes. MiR-19a, a component of the oncogenic miR-17-92 cluster, has been reported to be highly expressed only in anaplastic thyroid cancer, the most undifferentiated, aggressive and lethal form of thyroid neoplasia. In this work, we evaluated the putative contribution of miR-19a in de-differentiation and aggressiveness of thyroid tumors. To this aim, we induced miR-19a expression in the well-differentiated follicular thyroid cancer cell line and evaluated proliferation, apoptosis and gene expression profile of cancer cells. Our results showed that miR-19a overexpression stimulates cell proliferation and alters the expression profile of genes related to thyroid cell differentiation and aggressiveness. These findings not only suggest that miR-19a has a possible involvement in de-differentiation and malignancy, but also that it could represent an important prognostic indicator and a good therapeutic target for the most aggressive thyroid cancer.

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Gene Expression Analysis of PTEN Positive Glioblastoma Stem Cells Identifies DUB3 and Wee1 Modulation in a Cell Differentiation Model

Cited by 10 publications

References 20 publications

Resistance of papillary thyroid cancer stem cells to chemotherapy

Resistance of papillary thyroid cancer stem cells to chemotherapy

Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates

MiR-19a Overexpression in FTC-133 Cell Line Induces a More De-Differentiated and Aggressive Phenotype

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