0000000000217868
AUTHOR
Veronica Catalano
Therapeutic implications of Cancer Initiating Cells.
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…
CD133 as a target for colon cancer.
INTRODUCTION: Recent evidence based on cancer stem cell (CSC) models, is boosting the progress of translational research and providing relevant clinical implications in many tumour types, including colorectal cancer. The current failure of standard therapies is attributed to a small fraction of the primary cell population with stem-like characteristics, such as self-renewal and differentiation. Identification of CSCs is based on two different criteria of selection: stemness-selective conditions and direct isolation based on putative stem cell markers expression. CD133, a transmembrane glycoprotein, was associated with tumor-initiating cells derived from several histological variants of tumo…
CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.
SummaryCancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6− progenitor cells do not give rise to metastatic lesions but, when…
Normal vs cancer thyroid stem cells: the road to transformation
Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer develop…
Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling
Abstract Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2–D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and s…
Detection of Cancer Stem Cells Using AC133 Antibody
The cancer stem cell (CSC) model postulates that tumors are formed and maintained by a small population of undifferentiated cells, characterized by unique self-renewal properties and malignant potential. As CSCs survive chemotherapy inducing tumor recurrence, the specific targeting and eradication of these cells represents an important therapeutic challenge in cancer cure. Recent findings on CD133, a pentaspan transmembrane glycoprotein, discuss its application in the identification and isolation of SCs from cancerous tissues. However, the appropriateness of this protein constitutes an ongoing discussion. The expression pattern is debated and several issues highlight the need for additional…
Distinctive features of tumor-infiltrating γδ T lymphocytes in human colorectal cancer.
γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production…
Resistance of Cancer Stem Cells to Cell-Mediated Immune Responses
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…
Colorectal Cancer Stem Cells and Cell Death
Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem-like cells (CSCs), which survive conventional anticancer treatments, hanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) a…
Tumor and its microenvironment: a synergistic interplay.
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 …
Tumorigenic and Metastatic Activity of Human Thyroid Cancer Stem Cells
The recent discovery of CSCs as responsible for tumor development and progression has considerable therapeutic implications, since current cytotoxic drugs have a limited efficacy on CSCs and need to be replaced by target therapies. For this reason, much research effort has been addressed to identify and isolate CSCs as well as to improve understanding of the molecular mechanisms that control oncogenic process and chemotherapy resistance. Thyroid carcinomas are the most frequently diagnosed endocrine malignancy with a global increasing incidence. Data obtained during PhD course in Immunopharmacology showed that thyroid cancer tissues derived from follicular, papillary or anaplastic subtypes …
Human Thyroid Cancer Stem Cells
Increasing advances in stem cell research have opened new chances for treatment of many types of cancers. The identification of Cancer Stem Cells (CSCs) will provide a better knowledge of the molecular events governing carcinogenesis and the establishment of more accurate diagnostic methods and effective therapies. Parallel to other tumors, it has been demonstrated the presence of CSCs in thyroid cancers. Here, we will discuss the origin of human thyroid cancer stem cells and what is known about the molecular and the cellular aspects of their biology. We will also explore the potential traits of CSCs in thyroid cancer which give hope for the development of new therapeutic approaches in trea…
Estrogens and Stem Cells in Thyroid Cancer
Recent discoveries highlight the emerging role of estrogens in the initiation and progression of different malignancies through their interaction with stem cell compartment. Estrogens play a relevant role especially for those tumors bearing a gender disparity in incidence and aggressiveness, as occurs for most thyroid diseases. Although several experimental lines suggest that estrogens promote thyroid cell proliferation and invasion, their precise contribution in stem cell compartment still remains unclear. This review underlines the interplay between hormones and thyroid function, which could help to complete the puzzle of gender discrepancy in thyroid malignancies. Defining the associatio…