Modulation of low density lipoprotein receptor activity in squamous carcinoma cells by variation in cell density.
Morphological and biochemical studies on low density lipoprotein (LDL) receptor metabolism were performed in squamous carcinoma cells (SCC-15 and SCC-12F2). Modulation of terminal differentiation was achieved by culturing these cells at different cell densities. Studies on these cells cultured at low density (hardly any terminal differentiation) showed the following results: High affinity binding of LDL was excessive; LDL binding to SCC-15 cells was twice as high as that in SCC-12F2 cells and in fibroblasts. The distribution of the LDL binding visualized by LDL receptor antibodies was non-linear. There was no contact inhibition of LDL binding. LDL-gold particles were mainly bound to the plasma membrane outside coated pits. LDL-gold particles were internalized and delivered to dense bodies (= lysosomes). Degradation of LDL took place after a lag period of 10 min. Dissociation of LDL from the plasma membrane was substantial (more than 40% after a 120 min chase period). The same experiments on the cells cultured at high density (terminal differentiation present) showed several differences: A sharp decrease in high affinity LDL binding in both cell types. The internalization of surface bound LDL was defective in most of the squamous carcinoma cells. Dissociation of LDL from the plasma membrane was substantial, and after a chase period of 120 min at 37 degrees C still more than 20% of LDL remained intracellular and was not degraded. We postulate that LDL receptor-mediated endocytosis and degradation take place in squamous carcinoma cells but that during the process of terminal differentiation modulation of LDL-receptor metabolism occurs.(ABSTRACT TRUNCATED AT 250 WORDS)
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000648:ultrastructure; D002452:Cell Count; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003080:Cold Temperature; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D008077:Lipoproteins, LDL; D011973:Receptors, LDL