DISSECTING THE INDIVIDUALITY OF CANCER-CELLS - THE MORPHOLOGICAL AND MOLECULAR-DYNAMICS OF SINGLE HUMAN GLIOMA-CELLS

A glioma produces some of the most heterogeneously growing, angiogenic , and invasive primary brain tumor cells known. To dissect cellular in dividuality, and therefore tumor heterogeneity, multiple morphological and molecular processes in single living human glioma cells were meas ured using multimode light microscopy. Feature extraction of time-laps e image series of spreading, locomoting, and interacting cells either in the presence or absence of physiological modulators was performed b y defining five parameters that described cell shape, movement, and ce ll-cell contacts. Concurrent visualization of all five parameters with a scatterplot matrix revealed temporal as well as time-independent re lationships between the parameters that were sufficient to define the individuality of normal and transformed glial cells. Because the actin -cytoskeleton plays a role in regulating the cellular processes descri bed above, the dynamics of a fluorescent analog of nonmuscle actin wit hin motile glioma cells were measured in addition to the morphological parameters. The actin-cytoskeleton within the thin sweeping lamellipo dia of a glioma exhibited a paucity of large stress fibers, a rich col lection of microvillar structures containing actin, and dynamics that were distinct from those of normal motile cells. This approach can the refore potentially be used to dissect the molecular origins of transfo rmation using a small number of representative tumor cells. (C) 1996 W iley-Liss, Inc.