Matrix Metalloproteinases and Their Inhibitors in Squamous Cell Carcinoma of the Conjunctiva

Abstract

Squamous cell carcinoma of the conjunctiva (SCCC) belongs to a disease spectrum known as ocular surface squamous neoplasia (OSSN). Epidemiological evidence suggests that environmental ultraviolet radiation (UVR) exposure is the principal triggering agent. Despite this indirect evidence, the pathogenesis of SCCC remains poorly understood. We postulated that matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are upregulated in SCCC, and this could account for the invasive activity associated with this disease. Archival tissue specimens from 10 patients with SCCC were acquired to assess the expression of seven MMPs, three TIMPs, and two growth factors and their receptor by immunohistochemistry using specific antibodies. All MMPs and TIMP-2 were overexpressed in the tumor component compared to adjacent normal conjunctiva and cornea. Active MMP-7 was detected in diseased tissue, suggesting that at least some members of this family of enzymes are functionally involved. Moreover, active epidermal growth factor receptor (EGFR) and its ligands were detected within the tumor compartment. These data suggest that UVR-induced downstream cellular signaling events, including activation of cell-surface receptors and the induction of downstream effector molecules, such as MMPs and growth factors, are involved in the pathogenesis of SCCC. Mapping and inhibiting these pathways may aid in delineating the pathogenesis of SCCC and provide clues for optimizing current therapeutic methods or developing novel treatment strategies.