Cell Junctions and the Biological Behaviour of Cancer

: Quantitative and qualitative abnormalities in intercellular junctions have been described in a broad spectrum of human and animal cancers. Current efforts are aimed at exploring the possibility that some of these defects may account for the hallmarks of malignancy, namely tumour invasion and metastasis. This approach is hampered by a paucity of information on the natural history of human cancer. There is evidence from quantitative electron microscopy studies of urinary bladder carcinomas induced by a chemical carcinogen in Fischer rats that decreased intercellular adhesion, mediated in part by intercellular junctions, does not contribute to the invasive potential of tumours. However, it may account for increased cell shedding at the tumour surface. The increased leakiness of malignant epithelium is attributed to defects in occludens junctions. The defects appear to represent a failure to assemble intramembrane fibrils into fully competent occludens junctions, rather than a blockage of fibril synthesis. Gap junctional deficiencies are not an invariant in cancers. Further, gap junctional deficiencies are present in human cervical carcinoma-in-situ. These deficiencies are present many hundreds of cell generations before the development of invasive tumours. This argues against the hypothesis that gap junctions per se contribute to the biological behaviour (i.e. invasion) of malignant tumours.