Search results for "CANCER STEM CELL"

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

2014

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…

MYC Activates Stem-like Cell Potential in Hepatocarcinoma by a p53-Dependent Mechanism

2014

Activation of c-MYC is an oncogenic hallmark of many cancers including liver cancer, and is associated with a variety of adverse prognostic characteristics. Despite a causative role during malignant transformation and progression in hepatocarcinogenesis, consequences of c-MYC activation for the biology of hepatic cancer stem cells (CSCs) are undefined. Here, distinct levels of c-MYC over-expression were established by using two dose-dependent tetracycline inducible systems in 4 hepatoma cell lines with different p53 mutational status. The CSCs were evaluated using side-population approach as well as standard in vitro and in vivo assays. Functional repression of p53 was achieved by lentivira…

Abstract 3056: Lung tumor spheres as in vitro platform for testing new therapeutic strategies against cancer stem cells

2018

Abstract Background: Treatment resistance is related to cancer stem cells (CSCs), a highly tumorigenic subpopulation of cells capable of growing and forming tumor spheres under non-adherent conditions. This study aimed to isolate and characterise CSCs from resected non-small cell lung cancer (NSCLC) patients' tumor-tissue and cell lines like tumor spheres and to use them as an in vitro platform for drug screening. Methods: The study was performed on tumour cells from 8 resected NSCLC patients and 12 NSCLC cell lines grown in monolayer and as spheres. The expression of 60 genes, including CSC-markers, pluripotency inducers, cell cycle regulators and components of the Notch, Wnt and Hedgehog …

Abstract 3354: Characterization of lung tumorspheres by gene expression and flow cytometry: differential expression in CSC-related markers and signal…

2016

Abstract Chemoresistance, progression and metastasis have made of lung cancer the first cause of cancer mortality. These features were linked to a subpopulation of cells, named cancer stem cells (CSCs), which remain largely unknown. The aim of this study was to isolate and characterize CSCs from lung cancer cell-lines and tumor-tissue from resectable non-small cell lung cancer (NSCLC). Methods: Tumor cells from resected NSCLC and cell lines (H1650, H1993, A549, and PC9) were grown in monolayer and as spheroids. RTqPCR was performed to analyze the mRNA expression of CSCs-related genes: CSC-markers (EPCAM1, ALDH1A1, CD166, ABCG2, CD44, CD133); pluripotency genes (KLF4, OCT4, NANOG, SOX2, MYC,…

Human osteosarcoma 3AB-OS cancer stem cells is a model to study microRNA-29b-1 involvement in self-renewal and fate decisions of stem cells

2014

Resistance of Cancer Stem Cells to Cell-Mediated Immune Responses

2015

In the past decades, the hierarchical organization of tumors, governed by Cancer Stem Cells (CSCs), have been reported with regard to several tumor types. Advances in sequencing technologies have demonstrated that diverse genetic CSCs subclones, derived from the branching evolution, compete with each other within the tumor mass, thereby contributing to the functional heterogeneity. It is becoming increasingly clear that epigenetic modifications and microenvironmental influences are important determinants of tumor fitness resulting in disease progression, recurrence and reduced patient survival. Therefore, more effective therapies will require gaining insights into the role of genetic and no…

IL-4-mediated drug resistance in colon cancer stem cells

2008

Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently described as a reliable cancer stem-like cell marker in colon carcinoma. CD133+ cells are both necessary and sufficient to initiate tumour growth in animal models. The CD133+ cell population and spheroid cultures contain cells expressing the stem cell marker Musashi-1 which is involved in maintenance of stem cell fate in several tissues and importantly, this expression is maintained in stem-like cells…

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…

Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

2014

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differen…

3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study

2021

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with…