TRANS-MEMBRANE CONTROL OF RECEPTORS ON NORMAL AND TUMOR-CELLS .2. SURFACE CHANGES ASSOCIATED WITH TRANSFORMATION AND MALIGNANCY

The importance of the cell surface in certain neoplastic phenomena such as growth regulation, cell recognition, cell contact, metastasis, escape from host immune surveillance and other properties is relatively indisputable. None of the many observations on the dynamics and control of surface receptors of normal and tumor cells was able to explain completely the altered properties of tumor cells. This limitation is probably to be expected because of the complex nature of the phenomena and the systems under investigation. Tumor cells escape many of the controls and social restraints which subjugate normal cells, and they are able to achieve varying degrees of autonomy from their host. This autonomy results in uncontrolled proliferation, but it can also result in aberrant cell-to-cell recognition, allowing malignant tumor cells to escape from the control mechanisms which maintain proper cell position and prevent invasion of surrounding normal tissue. In malignant disease the surface properties of tumor cells are important not only in tissue invasion, but also in determining the subsequent patterns of cell distribution and establishment of distant metastases. Alterations in transmembrane communication and control mechanisms which probably maintain somewhat ordered, but dynamic, topographic displays or patterns of cell surface receptors on normal cells could contribute to loss of proper cell contact, recognition and positional information in tissues. Abnormal cellular properties of transformed cells such as contact inhibition, anchorage dependency, hormonal signaling, agglutinability, etc. are partly explainable by alterations in transmembrane communication and control mechanisms, perhaps mediated through cytoskeletal assemblages. Since proteolytic enzyme treatment appears to be capable of mimicking several transformed cell surface properties in normal cells, the prospect that enzyme-mediated dislocation of transmembrane controlling mechanisms resulting in a pleiotropic stimulus which initiates a wide range of cell surface and metabolic changes could account for many of the surface alterations accompanying neoplastic transformation has received wide attention. A high degree of speculation still surrounds the interpretation of cell surface data in this area, because of the lack of sufficient information. Cell research is still in its infancy and the relevancy of the observations discussed here with respect to the final control of neoplastic disease remains to be demonstrated.