Stromelysin‐3 expression is an early event in human oral tumorigenesis

Abstract

Key words: stromelysin; matrix metalloproteinase; oral cancerMMPs are a family of closely related Zn 2ϩ -dependent endopeptidases, involved in degradation of ECM and basement membrane in a substrate-dependent manner, leading to tumour invasion and metastasis. 1,2 In addition, MMPs play important roles in angiogenesis, tumour cell intravasation and malignant cell proliferation. 3,4 ST3, an MMP originally identified by its overexpression in primary breast carcinomas, 5 exhibits some characteristic features, including the inability to degrade any major ECM component, 6 intracellular processing of pro-ST3 by furin-dependent proteolytic cleavage and secretion in a potentially active form, 7 suggesting that it may have a unique role among the MMPs. Normal ST3 expression is associated with intense tissue remodelling during tissue involution, embryogenesis and wound healing. 8 -10 In a syngeneic tumorigenesis model in mice, ST3-increased tumorigenesis was shown to result from decreased cancer cell death through apoptosis and necrosis, suggesting that during malignancy the cellular function of ST3 is to favour survival of cancer cells in the stromal environment. 11 In most human cancers, ST3 expression has been observed in stromal fibroblasts surrounding malignant epithelial cells and suggested to promote tumorigenesis in a paracrine manner. 12,13 Strong ST3 expression has been correlated with increased aggressiveness of tumours and a poor clinical outcome. 14 In breast carcinomas, high levels of ST3 mRNA and protein correlated with poor clinical outcome. 15,16 ST3 expression was also observed in lung, colorectal and ovarian carcinomas. [17][18][19] Betel and tobacco consumption is the major cause of the high incidence of oral cancer, accounting for about 40% of all malignancies in the Indian subcontinent. SCC of the oral cavity is the most common cancer amongst Indian males and the third most common cancer among females. 20 The development of betel-and tobacco-associated oral SCC is a multistep process, clinically preceded by precancerous lesions, often leukoplakia, with histologic evidence of hyperplasia or dysplasia, the rate of malignant transformation being 5-10% over a period of 10 years. 21 Oral SCCs have a high potential for invasiveness leading to regional lymph node involvement and locoregional spread, causing severe morbidity. Elucidation of the factors affecting invasion and locoregional spread and identification of useful biomarkers to predict malignant potential are important for effective management of oral cancer. ST3 expression has been observed in head-and-neck cancer. 22,23 However, the role of ST3 in precancerous oral lesions remains to be comprehensively evaluated. Our aim was to determine the clinical significance of ST3 expression in early stages of oral tumour development and determine its relationship with intratumoral MVD as a parameter of angiogenesis. MATERIAL AND METHODS Tissue specimensOur study was approved by the Human Ethics Committee of the All India Institute of Medical Sciences (New D...

Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays

“…This protease has been described to be increased in a variety of cancer types, including breast (36), lung (37), and colon (38), particularly in the nonneoplastic fibroblasts surrounding the malignant epithelial cells. In contrast, expression of MMP11 in nasopharyngeal carcinoma seems to be restricted to the malignant epithelium, as also described in oral squamous carcinomas (39). This suggests that MMP11 represents a specific marker for carcinomas derived from the head and neck mucosa, a possibility that may warrant further exploration.…”

Study of matrix metalloproteinases and their inhibitors in prostate cancer

“…Normal MMP-11 expression is present during embryogenesis and wound healing, and its expression in stressed epithelial cells is detected in the vicinity of fibroblasts (Boulay et al, 2001). The MMP-11 expression is observed in the area that surrounds malignant epithelial tumour cells and sometimes in tumour cells of oesophageal, oral, papillary thyroid, colorectal, skin and ovarian carcinomas (Thewes et al, 1999;Mueller et al, 2000;Soni et al, 2003;Wasenius et al, 2003;Yamashita et al, 2004). Hence, MMP-11 gene expression seems to be associated with tumour progression (Basset et al, 1997).…”

Altered gene expression in conjunctival squamous cell carcinoma

“…27 Interestingly, MMP-11 protein has been demonstrated using immunohistochemistry in 70% of oral squamous cell carcinoma, where it is associated with lymph node involvement, but it is not a significant prognostic indicator. 28 Additional upregulated loci we identified previously associated with related cancers include collagen type I α1 (COL1A1), which is known to be induced in oral squamous cell carcinoma, where it has an important role in distinguishing oral squamous cell carcinoma from controls. 29 Our transcriptional profile analysis also showed upregulation of centromere protein F (CENPF) and hexokinase 2 (HK2), which are known to be overexpressed in esophageal 30 and cervical squamous cell carcinoma.…”