Journal of Supramolecular Structure and Cellular Biochemistry

Journal Information
ISSN / EISSN : 0275-3723 / 1547-1748
Published by: Wiley-Blackwell (10.1002)
Total articles ≅ 119
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Latest articles in this journal

Journal of Supramolecular Structure and Cellular Biochemistry, Volume 17;

Tatsuro Irimura, Garth L. Nicolson
Journal of Supramolecular Structure and Cellular Biochemistry, Volume 17, pp 325-336;

The role of glycoconjugates in cell surface and blood‐borne implantation properties of murine metastatic melanoma sublines of low (B16‐F1) or high (B 16‐F10) potential to colonize lungs was investigated by treating melanoma cells with the antibiotic tunicamycin. This drug prevents glycosylation of glycoproteins by inhibiting the formation of lipid‐linked oligosaccharide precursors. The degree of tunicamycin‐mediated modifications in glycoproteins was assessed by monitoring the decrease in cell surface sialogalactoproteins by binding of 125I‐labeled Ricinus communis agglutinin I. Scanning electron microscopy of tunicamycin‐treated B16‐F1 and B16‐F10 cells showed morphologic changes such as cell rounding and formation of numerous surface blebs. Tunicamycin‐treated B16‐F1 and B16‐F10 cells lost their lung colonization abilities when injected intravenously into C57BL/6 mice, concomitant with lowered rates of adhesion to endothelial cell monolayers, endothelial extracellular matrix (basal lamina), and polyvinyl‐immobilized fibronectin in vitro, suggesting that this drug inhibits experimental metastasis by modifying the surface glycoproteins involved in determining the adhesive properties of malignant cells.
Stuart H. Yuspa, Henry Hennings, Ulrike Lichti
Journal of Supramolecular Structure and Cellular Biochemistry, Volume 17, pp 245-257;

Mouse epidermal basal cells can be selectively cultivated in medium with a calcium concentration of 0.02–0.09 mM. Terminal differentiation and slouching of mature kcratinocytes occur when the calcium concentration is increased to 1.2–1.4 mM. When basal cell cultures are exposed to chemical initiators of carcinogenesis, colonies of cells that resist calcium‐induced differentiation evolve. Likewise, basal cells derived from mouse skin initiated in vivo yield foci that resist terminal differentiation. This defect in the commitment to terminal differentiation appears to be an essential change in initiated cells in skin and is also characteristic of malignant epidermal cells. This model system has also provided a means to determine if basal cells are more responsive to phorbol esters than other cells in epidermis and to explore the possibility that heterogeneity of response exists within subpopulations of basal cells. The induction of the enzyme ornithine decarboxylase (ODC) was used as a marker for responsiveness to phorbol esters. ODC induction after exposure to 12‐0‐tetradccanoylphorbol‐13‐acetate (TPA) in basal cells is enhanced 20‐fold over the response of a culture population containing both differentiating and basal cells. When basal cells are induced to differentiate by increased calcium, responsiveness to TPA is lost within several hours. In basal cell cultures, two ODC responses can be distinguished. After exposure to low concentrations of TPA or to weak promoters of the phorbol ester series, ODC activity is maximal at 3 hr. With higher concentrations of TPA, the ODC maximum is at 9 hr. These results arc consistent with the presence of subpopulations of basal cells with differing sensitivities to TPA. Other studies that use the enzyme epidermal transglutaminase as a marker for differentiation support this conclusion. In basal cell culture TPA exposure rapidly increases transglutaminase activity and cornified envelope development, reflecting induced differentiation in some cells. As differentiated cells arc sloughed from the dish, the remaining basal cells proliferate and become resitant to induced differentiation by 1.2 m M calcium. These data provide additional evidence of basal cell heterogeneity in which TPA induces one subpopulation to differentiate while another is stimulated to proliferate and resists a differentiation signal. Tumor promoters, by their ability to produce heterogeneous responses with regard to terminal differentiation and proliferation, would cause redistribution of subpopulations of epidermal cells in skin. Cells that resist signals for terminal differentiation, such as initiated cell, would be expected to increase in number during remodeling. Clonal expansion of the intitiated population could result in a benign tumor with an altered program of differentiation. In skin, benign tumors are the principal product of 2‐stage carcinogenesis. Subsequent progression to malignancy may involve an additional step, probably a genetic alteration, that is independent of the tumor promoter.
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