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Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

Deportment of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, 5 Ravdin, 3400 Spruce Street, Philadelphia, PA 19104

Sol S. Silverman, Jr

Oral Cancer Research Center, Department of Stomatology, University of California San Francisco, School of Dentistry, Box 0512, Room HSW-604, San Francisco, CA 94143-0512

Randall H. Kramer

Oral Cancer Research Center, Department of Stomatology, University of California San Francisco, School of Dentistry, Box 0512, Room HSW-604, San Francisco, CA 94143-0512, rkramer{at}itsa.ucsf.edu

It is the relentless invasion and growth into surrounding tissue that characterize oral squamous cell carcinoma. Metastasis is perhaps the most challenging and important aspect of cancer progression, in that it generally signifies limited survival and ineffective therapy. Inherent in metastasis is invasion, the process by which cells infiltrate into adjacent tissues, degrading basement membranes and extracellular matrix and disrupting tissue architecture and sometimes organ function. The factors that regulate these processes are complex and likely involve loss of the controls that are normally in place in physiologic tissue modeling. Adhesion receptors and their ligands are important in modulating not only invasion of oral squamous cell carcinoma cells but also their survival and proliferation. Normal oral mucosal epithelial cells use integrins to maintain their anchorage to the basement membrane, whereas the formation of stratifying cell layers depends on the formation of intercellular adhesions mediated by cadherins. The process of squamous cell carcinoma invasion and dissemination requires active cell migration through the extracellular matrix with the simultaneous remodeling of intercellular adhesions. Integrins are clearly important in the invasive process, whereas intercellular adhesion receptors restrain invasion and promote a more differentiated phenotype.

Key Words: Apoptosis • cadherin • extracellular matrix • integrin • invasion • metastasis.

Critical Reviews in Oral Biology & Medicine, Vol. 12, No. 6, 499-510 (2001)
DOI: 10.1177/10454411010120060401


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