Significance of stroma in biology of oral squamous cell carcinoma


The worldwide annual incidence of oral squamous cell carcinoma (OSCC) is over 300,000 cases with a mortality rate of 48%. This cancer type accounts for 90% of all oral cancers, with the highest incidence in men over 50 years of age. A significantly increased risk of developing OSCC exists among smokers and people who consume alcohol daily. OSCC is an aggressive cancer that metastasizes rapidly. Despite the development of new therapies in the treatment of OSCC, no significant increase in 5-year survival has been recorded in the past decades. The latest research suggests focus should be put on examining tumor stroma activation within OSCC, as the stroma may contain cells that can produce signal molecules and a microenvironment crucial for the development of metastases. The aim of this review is to provide an insight into the factors that activate OSCC stroma and hence faciliate neoplastic progression. It is based on the currently available data on the role and interaction between metalloproteinases, cytokines, growth factors, hypoxia factor and extracellular adhesion proteins in the stroma of OSCC and neoplastic cells. Their interplay is additionally presented using the Systems Biology Graphical Notation in order to sublimate the collected knowledge and enable the more efficient recognition of possible new biomarkers in the diagnostics and follow-up of OSCC or in finding new therapeutic targets.

Post author correction

Article Type: REVIEW



Vanja Vucicevic Boras, Aleksandra Fucic, Mihajlo Virag, Dragana Gabric, Igor Blivajs, Cedna Tomasovic-Loncaric, Zoran Rakusic, Vesna Bisof, Nicolas Le Novere, Danko Velimir Vrdoljak

Article History


Financial support: This project was supported by the Croatian Science Foundation under the title “The role of androgen and estrogen receptors in active stroma of oral cancer and their influence on patients’ survival” (I-1925-2015).
Conflict of interest: The authors have no conflicts of interest related to this article.

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  • Department of Oral Medicine, School of Dentistry, University of Zagreb, Zagreb - Croatia
  • Dental Department, Clinical Hospital Centre “Zagreb”, Zagreb - Croatia
  • Independent Researcher, Institute for Medical Research and Occupational Health, Zagreb - Croatia
  • Department of Oral and Maxillofacial Surgery, Clinical Hospital Centre “Dubrava”, Zagreb - Croatia
  • Department of Maxillofacial Surgery and Dentistry, Medical Faculty, University of Zagreb, Zagreb - Croatia
  • Department of Pathology, Clinical Hospital Centre Dubrava, Zagreb - Croatia
  • Department of Oncology, Clinical Hospital Centre “Zagreb”, Zagreb - Croatia
  • Department of Clinical Oncology, Medical Faculty, University of Zagreb, Zagreb - Croatia
  • Department for Nuclear Medicine and Oncology, Medical Faculty, University of Osijek, Osijek - Croatia
  • Biomathematics, Babraham Institute, Cambridge - UK
  • Department for Oncoplastic and Reconstructive Surgery, Clinic for Tumours, Clinical Hospital Centre “Sisters of Mercy”, Zagreb - Croatia

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