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 and the concomitant need for development of new therapeutic approaches will be discussed.
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu, Finland; Oulu University Central Hospital, Oulu, Finland; Institute of Dentistry, University of Helsinki, Helsinki, Finland. Electronic address: Tuula.salo@oulu.fi.
Tuula
T
Salo
Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978, Israel.
Marilena
M
Vered
Department of Oral Medicine and Diagnostic Sciences, King Saud University, Riyadh, Saudi Arabia.
Ibrahim O
IO
Bello
Oulu University Central Hospital, Oulu, Finland.
Pia
P
Nyberg
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu, Finland.
Carolina Cavalcante
CC
Bitu
Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978, Israel; Department of Oral and Maxillofacial Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Ayelet
A
Zlotogorski Hurvitz
Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978, Israel.
Dan
D
Dayan
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects*
D000970:Antineoplastic Agents
Antiangiogenesis; Carcinoma associated fibroblasts; Hypoxia; Inflammation; Oral cancer microenvironment; Oral cancer prognosis; Organotypic invasion assay; Proteases