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Changes in Plasma Membrane Structure Associated with Malignant Transformation in Human Urinary Bladder Epithelium¹

Department of Pathology, Rush Medical College, and Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612

Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive transitional cell carcinomas and invasive transitional cell carcinomas are shown to be significantly different. Using several statistical methods that test IMP topography vis à vis the random (Poisson) hypothesis, it is demonstrated that IMP are mildly aggregated in plasma membranes of normal human urothelial cells and that, in noninvasive carcinomas, IMP aggregation is increased. In invasive transitional cell carcinomas, IMP are statistically nonaggregated and are in a random distribution in the plane of the membrane. IMP numerical densities are also altered in the course of neoplastic transformation. IMP are significantly increased in number in plasma membranes in human noninvasive transitional cell carcinomas but are similar to control values in invasive tumors. Loss of IMP and changes in IMP topography may be related to tumor invasiveness or they may represent an epiphenomenon.

¹ Presented at the Conference "Early Lesions and the Development of Epithelial Cancer," October 21 to 23, 1975, Bethesda, Md. This work was supported by Grant CA-14447 from the National Cancer Institute, NIH, and by United States Air Force Contract F33615-75-R-5001 from the Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, Ohio. Early phases of this work were performed in the Department of Pathology, Tufts University School of Medicine, Boston, Mass.