Matrix Metalloproteinases and Their Inhibitors in Squamous Cell Carcinoma of the Conjunctiva
Authors
Nick Di Girolamo, Alp Atik, Peter J McCluskey, FRANZCO and Denis Wakefield
Institution
University of NSW
Country
Australia
Year
2013
Journal
Ocular Surface
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.