INVASION AND METASTASIS

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 physio logical functions including speech and swallowing. Additionally, in ma ny cases costly reconstructive surgery is required to repair the adver se cosmetic effects of the resective surgery. Thus, there is an urgent need to understand the molecular mechanism(s) which underlie the loca l and regional spread of this disease. Since the ability of tumor cell s to invade into surrounding structures requires hydrolytic action muc h 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 activa tor and several members of the collagenase family such as type I and I V collagenases and the stromelysins synthesized either by the tumor ce lls or in the surrounding fibroblasts. More recent studies have addres sed the mechanism(s) by which these hydrolases are overexpressed in in vasive cancer. In the tumor cells themselves, work has focused on defi ning the transcriptional requirements for enzyme synthesis and address ing how the appropriate transcription factors are activated by signal transduction pathways. In contrast, where the hydrolases (e.g. stromel ysin-2 and stromelysin-3) are produced by the fibroblasts, current inv estigations are directed at identifying tumor-derived growth factors w hich lead to the inducible expression of the enzymes in the stromal ce lls. The ultimate goal of these studies is to develop novel therapeuti c interventions which decrease the invasive capacity of head and neck cancer leading to longer survival times and enhanced quality of life f or patients afflicted with this disease.