Stimulation of tumor cell growth in vitro by a monoclonal antibody to a tumor specific protein (TSP-180) present on the cell surface of 3LL cells.
Proliferation capacity and MHC class I antigen expression of two Lewis lung carcinoma (3LL) metastatic variants (C87, BC215) grown under defined experimental conditions (serum-free defined medium or 10 per cent serum) have been studied following exposure to MoAb 135-13C which recognizes on these cells a tumor surface protein of 180,000 daltons (TSP-180). The results of this study indicate that the high metastatic clone (C87) binds higher amounts of MoAb to TSP-180 and Db antigens than does the low metastatic one (BC215), while both clones express very low amounts of Kb antigens. 3LL clones grown in 10 per cent serum or adapted in serum-free, defined medium show the same metastatic phenotype and MHC class I antigen expression, but when grown in defined medium exhibit increased capacity to bind MoAb 135-13C. However, the relative binding rate of 3LL clones grown in 10 per cent serum or in defined medium is unchanged: the high metastatic clone always showing higher capacity to bind MoAb to TSP-180. Furthermore, comparison of EGF binding sites on the cell surface of 3LL clones, grown in different culture conditions, demonstrates that the C87 clone binds higher amounts of labelled EGF and that this amount increases in serum-free defined medium, exactly as reported for TSP-180. In addition, competition experiments demonstrated that MoAb 135-13C does not compete for EGF binding sites on 3LL cell surface. Studies on cell proliferation following exposure to MoAb 135-13C, revealed that the low metastatic clone (BC215) is more actively stimulated than the high metastatic one. Moreover, similar data were obtained after exposure of 3LL clones to physiological amounts of different growth factors (i.e. EGF, MSA, insulin). Analysis of MHC class I antigen expression following exposure to MoAb 135-13C indicated that MoAb 135-13C induces on the cell surface of the C87 clone a transient low modulation of Db antigens. These results suggest that 3LL cells endowed with lower metastatic potential are more dependent on the microenvironmental conditions than the high metastasizing ones, and that MoAb 135-13C binding to 3LL cell surface stimulates proliferation as reported for several known growth factors.
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Istituto Regina Elena per lo studio e la cura dei tumori, Laboratorio di Biofisica, Roma, Italy.
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Kennel
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001667:Binding, Competitive; D004261:DNA Replication; D004815:Epidermal Growth Factor / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D039161:Integrin alpha6beta4; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D039161:Integrin alpha6beta4; D004815:Epidermal Growth Factor