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Title: Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes andmore » the concomitant need for development of new therapeutic approaches will be discussed. - Highlights: • Tumor depth and budding, hypoxia and TME cells associate with worse prognosis. • Pro-tumoral CAFs and CAI cells aid proliferation, invasion and spread hypoxia. • Some ECM-bound factors exert pro-angiogenic or pro-tumor activities. • Tumor spread is greatly dependent on ECM proteolysis, mediated by TME cells. • Direct targeting of TME components for treatment is still experimental.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [1] ;  [7] ;  [4] ;  [7]
  1. Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu (Finland)
  2. (Finland)
  3. Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan (Israel)
  4. (Israel)
  5. Department of Oral Medicine and Diagnostic Sciences, King Saud University, Riyadh (Saudi Arabia)
  6. Oulu University Central Hospital, Oulu (Finland)
  7. Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel)
Publication Date:
OSTI Identifier:
22416909
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 325; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; FIBROBLASTS; INFLAMMATION; LYMPHOKINES; MACROPHAGES; NATURAL KILLER CELLS; ORAL CAVITY; RECEPTORS; STEM CELLS