Comparative responses of normal and malignant mouse mammary cells to modulation of surface properties

We previously demonstrated that epithelial cells growing in primary cultures derived from normal and neoplastic mouse mammary tissues are indistinguishable on the basis of morphology, surface topography, agglutinability by concanavalin A, or of number, cytoplasmic location, or organization of microtubules and actin-containing microfilaments. In the present study, the modulation and interrelationships of these features were investigated using the drugs colchicine and cytochalasin B and the enzymes trypsin, collagenase, and hyaluronidase. Untreated cells of both types were only weakly agglutinable by concanavalin A. Pretreatment of the cells with colchicine, cytochalasin B, or hyaluronidase increased cytoagglutination by the lectin dramatically, whereas neither trypsin nor collagenase significantly altered reactivity of the cells. Binding studies utilizing fluorescein-tagged concanavalin A indicated that the enhanced agglutinability did not correlate with any particular distribution of lectin receptors on the cells. At the doses used, colchicine and cytocholasin B induced disruption of microtubules and microfilament networks, respectively, but no effects on either type of cytoskeletal element were observed after hyaluronidase, trypsin, or collagenase. The increased agglutinability was not associated with any specific surface conformation since scanning electron microscopy revealed that untreated cells and cells exposed to colchicine, hyaluronidase, and collagenase were flat and possessed variable numbers of small microvilli. In contrast, following incubation with cytochalasin B or trypsin, the cells underwent retraction and rounding, and developed complex surface structures such as blebs, ruffles, and filopodia. Thus, no single factor appeared responsible for determining the agglutinable or nonagglutinable state of the mammary cells. Morover, no differences were detected in the surface responses of the normal and malignant cells under any of the conditions used.