Summary
A 0.5% mineral-oil solution of 9.10-dimethyl-1.2-benzanthracene (DMBA) was applied to artificial cecal pouches in the lower lips of rats. Ultrastructural studies were made of plasma membranes and intercellular junctions during the process of malignant transformation in the oral mucosal epithelium and after squamous cell carcinoma had been induced by the carcinogen. After the administration of DMBA, the inner leaflet of the membranes where the microfilaments are attached showed high electron density and intramembranous particles on the P-face of basal cells decreased to about half that of controls. However, on the E-face the number of intramembranous particles increased by approximately 10% compared with controls. Though the normal size range for intramembranous particles was 9–12 nm, the administration of DMBA caused aggregations of from three to six particles on the P-face. In squamous cell carcinomas, only the outer leaflet of the membranes showed high electron density; the number of intramembranous particles was 30% higher on the P-face and approximately three times higher on the E-face compared with controls and the morphology of the intramembranous particles, which formed irregular aggregates of from five to 20 particles, was specific. In animals treated with DMBA, the number of gap junctions decreased by between 50% and 70%, although no structural changes occurred. In squamous cell carcinomas, the area of gap junctions was about 50% lower and the number of gap junctions about 40% lower than in controls. Changes in the number and area of desmosomes were similar to those of gap junctions both in the DMBA-treated animals and in squamous cell carcinomas.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alber RW (1976) The (sodium plus potassium) transport ATPase. In: Martonisi R (ed) The enzymes of biologic membrane. Wiley & Sons, Chichester, 3:283–301
Alory J, Weinstein RS, Pauli BU (1976) Relation of desmosome to tumour invasivness in human urinary bladder transitional carcinoma. Am J Pathol 82:31a
Azarnis A, Larsen WJ, Lowenstein WR (1974) The membrane junctions in communicating and non-communicating cells, their hybrids, and segregans. Proc Natl Acad Sci 71:880–884
Betlane M, Hermier B, Dubert JM, Paraf A (1976) Differences in the cell surface proteins of drug resistance and sensitive cell lines. Biochemie 58:731–736
Boschek CB, Jockusch BM, Friis RR, Back R, Grundman E, Bauer H (1981) Early changes in distribution and organization of microfilament proteins during cell transformation. Cell 24:175–184
Burger MW, Bombik BM, Breckenridge B, Sheppard JR (1977) Growth control and cycle alteration of cyclic AMP in the cell cycle. Nature 239:161–163
Carter SB (1967) Effects of cytocharasin on mamalian cells. Nature 213:261–264
Coman DR, Anderson TF (1955) A structure difference between the surface of normal and of carcinomatosis epidermal cells. Cancer Res 15:541–543
Davis AT, Estensen R, Quir PG (1971) Cytocharasin B: Inhibitation of human polyponuclear leukocyte phagocytosis. Proc Soc Exp Bio Med 137:161–164
Elias PM, Grayson S, Gross EG, Reck GL, McNutt NS (1981) Influence of topical and systemic retinoids on basal cell carcinoma cell membrane. Cancer 48:932–934
Farquhar MG, Palade G (1963) Junctional complexed in various epithelia. J Cell Biol 17:375–412
Flaxman BA, Cavoto FV (1973) Low resistant junctions in epithelial outgrowths from normal and cancerous epidermis in vitro. J Cell Biol 58:219–223
Franklin CD, Gohari K, Smith CJ, White FH (1980) Quantitative evaluation of normal, hyperplastic, and premalignant epithelium by stereological methods. In: Mackengie IC, Dabelstean E, Squor CA (eds) Oral premalignancy. Iowa State University Press, Ames, IA, pp 242–262
Fulker MJ, Cooper EH, Tanaka T (1971) Proliferation and ultrastructure papillary transitional cell carcinoma of the human bladder. Cancer 27:71–82
Grud JW, Evans WH (1973) Relative rate of degradation of mouse liver surface membrane proteins. Eur J Biochem 36:273–298
Hill M, Hillova J (1976) Genetic transformation of animal cell with viral DNA of RNA tumor viruses. Adv Cancer Res 23:273–298
Hruban Z, Mochizuki Y, Sleser A, Morris HP (1972) A comparative study of cellular organ of Morris hepatoma. Cancer Res 32:853–867
Hulser DF, Webb DJ (1973) Relation between ionic coupling and morphology of establish cells in culture. Exp Cell Res 80:210–222
Hynes RO (1976) Cell surface proteins and malignant transformation. Biophys Acta 457:57–108
Jonson RG, Shreiden JD (1971) Junctions between cancer cell in culture: ultrastructure and permeability. Science 174:717–719
Jonson RG, Hammer M, Schreiden JD, Revel JP (1974) Gap junction formation between reaggregation Novikoff hepatoma cells. Proc Natl Acad Sci 71:4573–4570
Kanno Y, Matui Y (1968) Cellular uncoupling in cancerous stomach epithelium. Nature 218:775
Lenard J, Singer SJ (1968) Alteration of conformation of proteins in red blood cell membrane in solution by fixations used in electron microscopy. J Cell Biol 37:117–121
Marchesi VT, Tillack TW, Jackson RL, Segrest JP, Scott RE (1972) Chemical characterization and surface orientation of the major glycoprotein of the human erythlocyte membrane. Proc Natl Acad Sci 69:1445–1449
McNutt NS, Weinstein RS (1971) Carcinoma of cervix; Deficiency of nexus intercellular junctions. Science 165:597–599
McNutt NS, Hershberg RA, Weinstein RS (1971) Further observation on the occurence of nexuses in benign and malignant human cervical epithelium. J Cell Biol 51:805–825
Mueller GC, Kensler TW, Kajiwara K (1978) Mechanism of DNA and chromatin relation; Possible targets of cocarcinogenesis. In: Slaga TJ, Silvak AB (eds) Carcinogenesis. Raven Press, New York 2:79–90
Nicolson GL (1974) The interaction of lectins with animal cell surfaces. Int Rev Cytol 39:89–195
O’Lague PO, Dalton H (1974) Low resistant junctions between normal and virous transformed fibroblast in tissue culture. Exp Cell Res 86:374–382
Olmsted JB, Borisey GG (1973) Microtubules. Ann Rev Biochem 42:175–184
Poole AR (1973) Tumor lysosomal enzymes and invasive growth. In: Dible JT (ed) Frontier biology; Lysosomes in biology and pathology. Elsevier North-Holland Biomedical Press, Amsterdam Oxford New York 29:303–337
Robertson TD (1963) The occurrence of a subunit pattern in the unit membrane of club ending in mauther cell synapsed in gold fish brains. J Cell Biol 19:201–221
Satir P, Satir B (1974) Partition coeffecient of membrane particles in the fusion rosette. Exp Cell Res 89:404–407
Shimono M, Clementi F (1977) Intercellular junctions of oral epithelium. II. Ultrastructure changes in rat buccal epithelium induced by trypsin digestion. J Ultrastruct Res 59:101–112
Singer S, Nicolson GL (1972) The fluid mosaic model of the structure of cell membrane. Science 175:720–731
Skov JC (1975) The (Na+-K+) activated enzyme system and its relationship to transport of sodium and potassium. Q Rev Biophys 7:401–434
Tachikawa T (1974) An experimental study of intraoral carcinogenesis. Especially penetration of carcinogens to carcinoma, by mean of fluorescence and electron microscopy. Shikagak- uho 74:781–803
Thoupoulos P, Roth T (1976) Insulin receptor in normal and transformed fibroblast; Relationship to growth and transformation. Cell 8:417–423
Wager R, Rosenberg M, Estensen R (1971) Endocytosis in changes liver cell quantiation by H-sucrose uptake and inhibitation by cytochalasin B. J Cell Biol 51:804–817
Wallach DFH (1968) Cellular membrane and tumor behavier, A new hypothesis. Proc Natl Acad Sci 61:868–874
Weinstein RS, McNutt NS (1970) Ultrastructure of red cell membrane. Semin Hematol 7:259–274
Weinstein RS, Merk FB, Alroy J (1976) The structure and function of intercellular junctions in cancer. Adv Cancer Res 23:23–89
Wood DA, Smith CJ (1970) Ultrastructure and development of epithelial pseudopodia in chemically induced premalignant lesions of the hamster cheek pouch. Exp Mol Pathol 12:160–174
Yamamura T, Nishida Y, Eda S, Shimono M, Yamane H, Tachikawa T, Koike H, Ichikawa T, Yoshida M, Watanabe O, Matsuyama H (1975) An experimental study of intraoral carcinogenesis in rats. Oral Surg Oral Med Oral Pathol 39:87–102
Yen S, Chen HC, How SW, Denz CZ (1974) Fine structure of Bowen’s disease in chronic arsenicalism. J Nat Cancer Inst 53:31–33
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tachikawa, T., Yamamura, T. & Yoshiki, S. Changes occurring in plasma membranes and intercellular junctions during the process of carcinogenesis and in squamous cell carcinoma. Virchows Archiv B Cell Pathol 47, 1–15 (1984). https://doi.org/10.1007/BF02890184
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02890184