Mediators of extracellular matrix degradation and inflammation: A new team of possible biomarkers for oral squamous cell carcinoma stage

Exp Ther Med. 2021 Aug;22(2):877. doi: 10.3892/etm.2021.10309. Epub 2021 Jun 15.

Abstract

Oral cancer represents one of the most common types of cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most frequently diagnosed. Cytokines play a crucial role in inflammation, apoptosis and metastasis. Interleukin (IL)-8 promotes the direct migration of inflammatory cells. IL-6 induces tumor cell proliferation, increases expression of invasiveness and angiogenetic factors or matrix metalloproteinases (MMPs), promoting metastasis. Tissue inhibitor of metalloproteinases (TIMPs) blocks the action of MMPs controlling extracellular matrix degradation and inhibiting metastasis. The aim of our study was to analyze the existence of correlations between inflammation markers (IL-6 and IL-8) and extracellular degradation protection markers such as TIMP-1 in OSCC tumors. Our study included 20 patients (12 females and 8 males) diagnosed with OSCC, recruited from January to April, 2020. IL-8, IL-6 and TIMP-1 levels were measured in the tumor cell lysates by ELISA technique, using relevant assay kits. Our results showed a positive and significant correlation between IL-6 and IL-8 (P=0.005, R=0.517) indicating that high IL-8 levels can be associated with high IL-6 levels. We also found a significant and high negative correlation (P<0.001, R=-0.673) between IL-6 and TIMP-1 and a significant and high negative correlation (P<0.001, R=-0.684) between IL-8 and TIMP-1 indicating that high levels of IL-8 and IL-6 are significantly associated with lower levels of TIMP-1. In conclusion, our study confirms the available literature data on IL-6 and IL-8 as potential markers for oral cancers such as OSCC and affect the tumor microenvironment by decreasing TIMPs. All three biomarkers included in this study have the potential to be used as detection or prognostic factors for oral cancer.

Keywords: IL-6; IL-8; MMP; TIMP-1; cellular matrix degradation; inflammation; oral cavity; squamous cell carcinoma.

Grants and funding

Funding: This paper was financially supported by ‘Carol Davila’ University of Medicine and Pharmacy (contract no. 23PFE/17.10.2018) funded by the Ministry of Research and Innovation within PNCDI III, Program 1-Development of the National R&D system, Subprogram 1.2-Institutional Performance-RDI excellence funding projects.