The invasive character of
squamous cell carcinoma of the head and neck represents a major challenge to the clinician since most often these
tumors require extensive surgical resection impairing important physiological functions including speech and swallowing. Additionally, in many cases costly reconstructive surgery is required to repair the adverse cosmetic effects of the resective surgery. Thus, there is an urgent need to understand the molecular mechanism(s) which underlie the local and regional spread of this disease. Since the ability of
tumor cells to invade into surrounding structures requires hydrolytic action much effort has been spent on identifying the
hydrolases involved in this process. Some of the
enzymes which have been implicated in the spread of
head and neck cancer include the
urokinase-type plasminogen activator and several members of the
collagenase family such as type I and IV
collagenases and the stromelysins synthesized either by the
tumor cells or in the surrounding fibroblasts. More recent studies have addressed the mechanism(s) by which these
hydrolases are overexpressed in invasive
cancer. In the
tumor cells themselves, work has focused on defining the transcriptional requirements for
enzyme synthesis and addressing how the appropriate
transcription factors are activated by signal transduction pathways. In contrast, where the
hydrolases (e.g.
stromelysin-2 and
stromelysin-3) are produced by the fibroblasts, current investigations are directed at identifying
tumor-derived
growth factors which lead to the inducible expression of the
enzymes in the stromal cells. The ultimate goal of these studies is to develop novel therapeutic interventions which decrease the invasive capacity of
head and neck cancer leading to longer survival times and enhanced quality of life for patients afflicted with this disease.