MMP-9 as a potential biomarker for carcinoma of oral cavity: a study in eastern India

Abstract

Carcinoma of oral cavity have a high risk of recurrence after initial treatment with surgery, radiotherapy, surgery with adjuvant radiotherapy, or radio-chemotherapy.The present study investigated the changes in expression, activity and regulation of matrix metalloproteinases (MMP) -2 and -9 in oral squamous cell carcinoma (OSCC) which might help to ascertain the invasive potential of the tumor .Tumor tissues and adjacent normal tissues of OSCC patients [N,37; either sex; 20-70 yrs] were subjected to clinico-pathology, histopathology and TNM grading. The enzyme activity and associated signalling was observed with gelatin zymography, immunohistochemistry, ELISA, western blot and semi quantitative reverse transcriptase PCR.OSCC tissues were observed with elevated MMP-9 activity, enhanced expression of fibronectin (FN), phosphorylated focal adhesion kinase (FAK Try 397), phosphatidyl inositol 3-kinase (PI3K), protein kinase B (AKT) and reduced expression of tissue inhibitor of metalloproteinase-1(TIMP-1) than the control tissues.OSCC patients elicited a predominance of MMP-9 activity via up regulated FAK/PI3K/AKT pathway. A routine MMP-9 analysis may ascertain the invasiveness of the tumor and therefore may be professed as a suitable biomarker for metastatic potential of oral cancer. Key words: oral squamous cell carcinoma, MMP-9, zymography, eastern IndiaIn India, oral cancer forms a large group of malignancy representing 30-40% of all cancers [1]. By the year 2020 cancers of the mouth (64,525; 29.5%), tongue (38,052; 17.4%) and larynx (33,855,15.5%) will be the major sites of oral cancer [2].The frequency of oral malignancy varies between Indian states which might be due to regional differences in disease-specific risk factors [3]. The pattern of cancer incidence in rural West Bengal showed that the oral cavity, pharynx, larynx contributed to more than half of the cancers in men and about a quarter in women. Indigenous habits of chewing and smoking seemed to be primarily responsible for their high incidence [4].Oral squamous cell carcinoma (OSCC) is one of the deadliest forms of oral malignancy which is associated with high morbidity and mortality, resulting from local, regional and distant metastasis [5]. This creates a great concern for scientists and prioritizes the search for suitable biomarker of oral cancer.Matrix metalloproteinases (MMPs) are the principal mediators for the degradation of extracellular matrix (ECM) components which take place during the invasion and metastasis [6,7]. MMPs are zinc dependent family of endopeptidases and the gelatinases, MMP-2 (Gelatinase A, 72 KDa) and MMP-9 (Gelatinase B 92 KDa), are the master molecules for the malignant phenotype because of their unique property to degrade type IV collagen, a major component of the basement membrane [8].The orchestra of signaling molecules associated with MMP regulation is highly complicated. In areas with basement membrane defects the invading carcinoma cells may come in contact with the abundant stromal fibronectin (FN) matrix. The 12...

Role of Chemokine and TNF signaling pathway in oral squamous cell carcinoma: A RNA deep sequencing analysis of oral buccal mucosa squamous carcinoma model of Chinese hamster

“…Its main function is to degrade and remodel the ECM, maintain the dynamic balance of ECM, and participate in many pathological and physiological processes in the body. Many of clinical studies have confirmed the high expression of MMP9 and MMP13 in OSCC (Jingqiu et al, 2015; Monteiro et al, 2016; Nanda et al, 2014), which is consistent with our research. Monteiro (Monteiro et al, 2016) applied immunohistochemistry to detect the expression of MMP9 protein in 60 cases of OSCC and found that MMP9 was strongly expressed in cytoplasm of tumor cell in 83.7% of patients, suggesting that MMP9 is a potential tumor marker of oral cancer.…”

Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells

“…In this study, we found that the TIMP1 gene expression in SAS cells cultured in ALG was significantly lower than that in 2D cells and there was no significant difference in TIMP1 gene expression between ALG and ALG-CS ( Fig. S9a ), which was consistent with the report on TIMP1 in oral squamous cell carcinoma tissues 41 . In addition, we found that higher expression of TIMP1 gene in the 3D-cultured LM3 cells ( Fig.…”

A circular RNA derived from MMP9 facilitates oral squamous cell carcinoma metastasis through regulation of MMP9 mRNA stability

“…Accumulating evidence suggests that MMP9 plays a key positive regulator in OSCC cell migration and invasion across basement membranes 6 . OSCC patients with high MMP9 expression are closely associated with metastatic clinical features and worse prognosis 7 . Although the important biological functions of MMP9 have been clearly elucidated, the mechanism of its dysregulation is still unclear.…”