Early metastasis of human solid tumours: expression of cell adhesion molecules

Loss and gain of cell surface molecules determines the mobilization, emigration and invasiveness of epithelial cancer cells. As a first approach to gain further insight into these processes, we have followed two strategies: (1) to identify tumour cells which have disseminated early from primary carcinomas and to obtain information about the phenotype and prognostic significance of these cells; and (2) to identify molecular changes occurring in primary tumour cells at the time they develop their metastatic potential. Our analyses indicate that changes in the adhesive properties of solid tumour cells, such as down-regulation of desmosomal proteins (e.g. plakoglobin) and neo-expression of ICAM-1 or MUC18, are important determinants of the metastatic capability of individual malignant cells. The expression pattern of these cell adhesion molecules during tumour progression appears to reflect a disturbance at the level of the molecular elements normally responsible for controlling their expression. The outlined current strategies for detection, characterization and antibody therapy of cancer micrometastasis can be applied to the secondary prevention of metastatic disease in patients with minimal residual cancer.