No abstract

Membrane permeability of an epithelial cell junction (Drosophila salivary gland) was examined with intraccllular microclectrodes and with fluorescent tracers. In contrast to the non-junctional cell membrane surface, which has a low permeability to ions (I0 -4 mho/cm2), the junctional membranc surface is highly pcrmcable. In fact, it introduces no substantial restriction to ion flow beyond that in the cytoplasm; the resistance through a chain of cells (150 ~ cm) is only slightly greater than in extrudcd cytoplasm (100 ~ cm). Thc diffusion resistance along thc intcrccllular spacc to the cxtcrior, on thc other hand, is very high. Here, there exists an ion barrier of, at least, 10 4 ~ cm 2. As a result, small ions and fluorescein move rather freely from one cell to the next, but do not leak appreciably through the intercellular space to the exterior. The organ here, rather than the single cell, appears to be the unit of ion environment. The possible underlying structural aspects are discussed.

In four epithelial cell systems (salivary gland, renal, urinary bladder, and sensory cells) cells are interconnected as far as much of their ion content is concerned. In the salivary gland and renal epithelia, all cells of the epithelium are interconnected; and communication between a given cell and any of its nearest neighbors is equally good. In the bladder and sensory epithelia, communication appears to be more restricted, manifesting itself in chains of connected cells in the former, and in small groups of connected cells in the latter. The permeability of the cell membrane at the junction between connected cells is several orders of magnitude greater than it is at the cell surface bordering the exterior of the cells. Each connected cell ensemble functions as a system with a fairly continuous cytoplasmic core bounded by a diffusion barrier which is continuous along the entire outer surface of the system. As a result, ions move rather freely from cell to cell, but not from cell interior to exterior. Intercellular communication in at least three epithelia is associated with the presence of certain close-junctional membrane complexes.

A B S T R A C TIntercellular communication was examined with intracellular electrical techniques in prim a r / a n d transplanted rat liver cancers. Normal liver cells communicate rather freely with each other through permeable junctional membranes. Cancer liver cells show no communication at all; their surface membrane is a strong barrier to diffusion all around the cell.Cancer cells induce alterations in membrane permeability in normal liver ceils; communication among the latter is markedly reduced when cancer cells grow near them. I N T R O D U C T I O NEvidence for direct cell-to-cell communication is now availablc for a wide variety of epithelial tissues (12, 12 a, 17). At the surfaces of cell contact (junctional surfaces), the cell membranes in, at least, some of these tissues are normally so permeable that many cellular substances may diffuse rather freely from one cell interior to the next. The present series of papers deals with the question of whether cellular communication of this sort is involved in the control of tissue growth.It has long been evident that normal growth of tissues depends on some form of contact interaction between cells. Harmonious growth requires, among other things, that cells recognize each other and stop moving and growing atthe right place. Instructive, in this respect, is the movement of epidermal cells over a wound; the movement stops when the cells meet (10). Particularly instructive is the behavior of cells in tissue culture growing on glass surfaces. The cells stop moving and dividing when they establish contact with each other, and stop only then (1, 24). Some kind of signal appears to be transmitted from cell to cell upon contact. The question here, then, is whether diffusion of substances from cell interior to cell interior is involved in the signal transmission.A direct approach to the question seems hopeless until specific signal substances are identified. But one may try an indirect approach and see whether cellular communication is altered in situations of uncontrolled cellular growth. Here, we shall explore this point in cells showing the most notorious lack of growth control, cancer cells. Cancer cells, unlike normal ones, neither stop moving nor dividing upon cellular contact, as is seen particularly clearly in tissue culture (2, 5-7, 23a).