Search results for "Neoplastic stem cells"
showing 10 items of 134 documents
Aldehyde Dehydrogenase 1-Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
2009
Abstract Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer. Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank …
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.
2008
The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demons…
Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids
2021
AbstractThe prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display…
Tumor and its microenvironment: a synergistic interplay.
2013
The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species …
Collecting evidence for a stem cell hypothesis in HCC.
2010
Ever since Ernest McCulloch and James E Till defined essential stem cell properties, the field of stem cell biology has attracted increasing interest.1 Manipulating embryonic stem cells has resulted in advanced genetic technologies such as knock-out and transgenic animals, providing valuable models to study genetic influence on a wide variety of diseases.2 The success in manipulating stem cells and the ability to differentiate them into diverse tissues brought with them countless concepts of utilising stem cells in medicine. The idea of perpetually dividing pluripotent cells, capable of differentiating into nearly every possible cell or tissue type, seems like an inexhaustible resource for …
Molecular diagnosis and therapy of hepatocellular carcinoma (HCC): an emerging field for advanced technologies.
2011
Despite great progress in diagnosis and management of hepatocellular carcinoma (HCC), the exact biology of the tumor remains poorly understood overall limiting the patients' outcome. Detailed analysis and characterization of the molecular mechanisms and subsequently individual prediction of corresponding prognostic traits would revolutionize both diagnosis and treatment of HCC and is the key goal of modern personalized medicine. Over the recent years systematic approaches for the analysis of whole tumor genomes and transcriptomes as well as epigenomes became affordable tools in translational research. This includes simultaneous analyses of thousands of molecular targets using microarray-bas…
Colon Cancer Stem Cells: Promise of Targeted Therapy
2010
First developed for hematologic disorders, the concept of cancer stem cells (CSCs) was expanded to solid tumors, including colorectal cancer (CRC). The traditional model of colon carcinogenesis includes several steps that occur via mutational activation of oncogenes and inactivation of tumor suppressor genes. Intestinal epithelial cells exist for a shorter amount of time than that required to accumulate tumor-inducing genetic changes, so researchers have investigated the concept that CRC arises from the long-lived stem cells, rather than from the differentiated epithelial cells. Colon CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed…
Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.
2008
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear β-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling…
Therapeutic implications of Cancer Initiating Cells.
2009
Background: Until few years ago, all neoplastic cells within a tumour were suggested to have tumorigenic capacity, but recent evidences hint to the possibility that such feature is confined to a subset of Cancer Initiating Cells (CICs), also called Cancer Stem Cells (CSCs). These cells are the reservoir of the heterogeneous populations of differentiated cancer cells constituting the tumour bulk. Mechanisms shared with somatic stem cells, such as quiescence, self-renewal ability, asymmetric division and multidrug resistance, allow to these cells to drive tumour growth and to evade conventional therapy. Objective: Here, we give a brief overview on the origin of CICs, the mechanisms involved i…
Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer.
2015
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a …