Journal of Cytology & Tissue Biology Category: Clinical Type: Review Article
Inducers of Epithelial Mesenchymal Transiton and Cancer Stem Cells in Malignant Pleural Effusions
- Emanuela Cherubini1*, Enrico Giarnieri2, Alberto Ricci2, Salvatore Mariotta1, Maria Rosaria Giovagnoli2, Rita Mancini3
- 1 Department Of Clinical And Molecular Medicine, Sapienza University Of Rome, Rome, Italy
- 2 Department Of Clinical And Molecular Medicine, Azienda Ospedaliera Sant'Andrea, Sapienza University Of Rome, Rome, Italy
- 3 Department Of Clinical And Molecular Medicine, Laboratory Of Research And Diagnostics, Sapienza University Of Rome, Rome, Italy
*Corresponding Author:Emanuela Cherubini
Department Of Clinical And Molecular Medicine, Sapienza University Of Rome, Rome, Italy
Received Date: Sep 16, 2016 Accepted Date: Nov 01, 2016 Published Date: Nov 14, 2016
The Epithelial to Mesenchymal Transition (EMT) plays a role not only in tumor metastasis but also in tumor recurrence. This process is believed to be tightly linked to the presence of Cancer Stem Cells (CSCs) however, it is still not clear which factors could induce EMT and how it could be a source for CSCs. It has been demonstrated that Malignant Pleural Effusion (MPEs) may represent an excellent source to identify markers and molecular mechanisms involved in EMT and CSCs development. Growth factors, cell differentiation markers and molecular adhesion are involved in some of the crucial neoplastic cell events such as proliferation, metastasis, resistance to chemotherapy and EMT.In this review, we summarize the current understanding of which molecular markers can orchestrate EMT and CSCs in MPEs.
Lung cancer has produced the highest mortality rate in the world, current therapy is relatively ineffective and the survival rate at 5 years is still only 15% for the advanced disease. The presence of neoplastic cells in the pleural fluid represents a common medical problem in cancer patients with advanced neoplastic disease and it leads to poor survival [1-8]. Lung and breast cancers cause approximately 75% of all MPE. However, for around 10% of MPE cases, the primary tumor is unknown [9-13]. In MPEs it has been observed that neoplastic cells produce factors that contribute to overcoming the protective mesothelial layer. For example, neoplastic cells are capable of internalizing the CD44-hyaluronan complex and hydrolyzing it in oligosaccharides showing increased permeability in the mesothelial layer and angiogenic chemotactic ability . Furthermore, VEGF and bFGF produced by neoplastic cells increase the permeability of the pleural surface ; a low level of endostatin observed in patients with malignant pleural effusion increases endothelial cell migration, angiogenesis and tumor growth . Microenvironment, hypoxia and chemokines can modify the mesothelial cell phenotype. The ability of these cells to switch dynamically between different phenotypic states led to a series of studies in which different Authors demonstrated that MPEs could be an excellent source in cancer biology investigation and the identification of potential target therapy solutions. Following this, studies identified the presence of small-sub-populations of cells, also named cancer stem cells or cancer initiating cells, within the tumor cells, causing the aggressive behaviour of cancer cells [17-19]. The presence of these sub-populations, capable of self-renewal and multipotent differentiation, could add a new element in cancer research, explain the concept of heterogeneity, relapse after treatment and resistance to conventional chemotherapies.
INDUCERS OF EMT
Vimentin and LASP-1
Snail and slug
Neurotrophins and TrK receptors
CANCER STEM CELL MARKERS
The identification of more efficient therapies for the treatment of malignant pleural effusion in patients with metastatic lung cancer is crucial to understand the mechanisms that cause current fail treatment. Characterization of CSCs in malignant pleural effusion and recent understanding of EMT contributed to better know about environment, behavior and prognosis of this tumor. Advances have been made towards elucidating causes and mechanisms of EMT in malignant pleural effusion considering EMT process as one of possible mechanisms through which CSCs are generated. However, beyond identification and characterization of cell surface markers, there is still much that remains unknown about CSCs and EMT interaction including the mechanisms they utilize to maintain their chemoresistance.
This work was supported by AIRC Grant IG 17009 to R. Mancini.
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Citation:Cherubini E, Giarnieri E, Ricci A, Mariotta S, Giovagnoli MR et al. (2016) Inducers of Epithelial Mesenchymal Transiton and Cancer Stem Cells in Malignant Pleural Effusions. J Cytol Tissue Biol 3: 011.
Copyright: © 2016 Emanuela Cherubini, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.