Search results for "cancer stem cell"

Novel Approaches for Glioblastoma Treatment: Focus on Tumor Heterogeneity, Treatment Resistance, and Computational Tools

2019

BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain tumor. Currently, the suggested line of action is the surgical resection followed by radiotherapy and treatment with the adjuvant temozolomide (TMZ), a DNA alkylating agent. However, the ability of tumor cells to deeply infiltrate the surrounding tissue makes complete resection quite impossible, and in consequence, the probability of tumor recurrence is high, and the prognosis is not positive. GBM is highly heterogeneous and adapts to treatment in most individuals. Nevertheless, these mechanisms of adaption are unknown. RECENT FINDINGS: In this review, we will discuss the recent discoveries in molecular and cellular heterog…

The Role of SVZ Stem Cells in Glioblastoma

2019

As most common primary brain cancer, glioblastoma is also the most aggressive and malignant form of cancer in the adult central nervous system. Glioblastomas are genetic and transcriptional heterogeneous tumors, which in spite of intensive research are poorly understood. Over the years conventional therapies failed to affect a cure, resulting in low survival rates of affected patients. To improve the clinical outcome, an important approach is to identify the cells of origin. One potential source for these are neural stem cells (NSCs) located in the subventricular zone, which is one of two niches in the adult nervous system where NSCs with the capacity of self-renewal and proliferation resid…

Advances in Targeting Signal Transduction Pathways

2012

// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Lin Sun 1,2 , Nicole M. Davis 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Lucio Cocco 3 , Camilla Evangelisti 4 , Francesca Chiarini 4 , Alberto M. Martelli 3,4 , Massimo Libra 5 , Saverio Candido 5 , Giovanni Ligresti 5 , Grazia Malaponte 5 , Maria C. Mazzarino 5 , Paolo Fagone 5 , Marco Donia 5 , Ferdinando Nicoletti 5 , Jerry Polesel 6 , Renato Talamini 6 , Jorg Basecke 7 , Sanja Mijatovic 8 , Danijela Maksimovic-Ivanic 8 , Michele Milella 9 , Agostino Tafuri 10 , Joanna Dulinska-Litewka 11 , Piotr Laidler 11 , Antonio B. D’Assoro 12 , Lyudmyla Drobot 13 , Kazuo Umezawa 14 , Giuseppe Montalto 15 , Melchiorre Cer…

Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination

2020

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10−16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial–mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs…

Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.

2009

Abstract Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant int…

Colorectal Cancer Stem Cells: From the Crypt to the Clinic

2014

Since their first discovery, investigations of colorectal cancer stem cells (CSCs) have revealed some unexpected properties, including a high degree of heterogeneity and plasticity. By exploiting a combination of genetic, epigenetic, and microenvironmental factors, colorectal CSCs metastasize, resist chemotherapy, and continually adapt to a changing microenvironment, representing a formidable challenge to cancer eradication. Here, we review the current understanding of colorectal CSCs, including their origin, relationship to stem cells of the intestine, phenotypic characterization, and underlying regulatory mechanisms. We also discuss limitations to current preclinical models of colorectal …

Do nonmelanoma skin cancers develop from extra-cutaneous stem cells?

2008

A hypothesis is presented that nonmelanoma skin cancers can develop from extra-cutaneous stem cells, and not exclusively from skin keratinocytes. This idea is supported by recent findings regarding the initiation of cancers in the digestive tract, and by a cancer stem cell model of a neoplasia. It is known that multipotent adult progenitor cells can trans-differentiate into very diverse cellular lineages and can be recruited to areas of profound tissue injury. In these settings, they might also initiate malignant transformation. Some epidemiological data and recent findings regarding mechanisms of wound healing indicate that skin cancers could also originate from bone marrow-derived or othe…

Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma.

2017

Hepatocellular carcinomas (HCC) contain a subpopulation of cancer stem cells (CSCs), which exhibit stem cell–like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem-cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic-cell reprogramming. Here, we focused on the role played by the histone variant macroH2A1 as a potential epigenetic factor promoting CSC differentiation. In human HCC section…

THE TUMOR CELL IDENTITY: A GATEWAY TO THE MOLECULAR BASIS OF MALIGNANT TRANSFORMATION

It is now well established that within a tumor mass there is a hierarchical organization, stemming from a cell subpopulation retaining the highest tumorigenic potential, referred as cancer stem cells (CSCs), responsible for tumor initiation and progression. Although recent advances in stem cell biology led to the acquisition of new view of thyroid carcinoma as a stem cell disease, the cellular origin of thyroid CSCs remains unknown. In Chapter 1 it is critically discussed the potential role of thyroid stem cells (TSCs) in light of the available information on the oncogenic role of genetic alterations underlying the thyroid carcinogenesis. Understanding the key events that regulate thyroid t…

p63 Isoforms Regulate Metabolism of Cancer Stem Cells

2014

p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (ΔN) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and ΔNp63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or ΔNp63 isoforms, to carry out a proteomic study by chemical-labeling …