Functional Significance of Microtubules and Microfilaments for Cellular Motility in Cultured Brain Tumors

The cytoplasmic fibrillar system, microtubules and microfilaments (MT & MF), has been known to control several aspects of cell functions, such as motility, configuration and various membrane activities. The author utilized the cell motility and configuration as the indicator for the evaluation of MT & MF functions in cultured benign and malignant brain tumors. The cellular motility was studied by continuous monitoring of the cultured cell locomotion through a computerized autotracking microscope. The data were analysed by a computer using electric address signals obtained 60 times per second from a television camera. Morphological investigation of the cell configuration consisted of serial photography of the TV monitor and electron microscopy of the fixed cells. These observations were performed before, during and after perfusion of the cultured cells with a normal culture media and various chemical solutions which affect MT & IF functions. Motility of the cell was expressed as the mean motility which is a sum of distances (X and Y components) in an unit time. When RG -C6 (mouse glioma) cells and cultured human brain tumor cells were exposed to cytochalasin B (an inhibitor of microfilaments), the cell shape and locomotion were affected significantly. The motility of the cells increased remarkably as much as 2,000% in malignant astrocytomas and 300% in benign astrocytomas. Morphologically, ruffling of the mean cytoplasmic membrane disappeared, and the leading edge then retracted. These changes associated with the cytochalasin B perfusion were dose dependent, occurred promptly and were fully reversible. However, these changes were not observed with colchicine (an inhibitor of the microtubular function) treatment of the cell. A significant difference was observed in the degree of the rate of motility increase between the cultured human malignant astrocytoma cells and the benign astrocytoma cells. The author postulated that the difference between benign and malignant type cells is probably related to a difference in the quality of the microfilament rather than quantity, since the difference is calculated as a ratio between pre- and post perfusion values. Functions of microfilaments and microtubules in the brain tumor cells and the relation of these functions to the clinical malignancy of the brain tumor were discussed