Abstract
Sarcoma cells growing in tissue culture have morphological and growth characteristics different than normal fibroblasts. Several of the morphological characteristics of normal fibroblasts are regained when the cells are incubated with dibutyryl-cyclic AMP or butyryl-cyclic AMP (0.1-1 mM), or cyclic AMP (3 mM) plus theophylline (1 mM), but not with ATP, ADP, AMP, adenine, or adenosine (1-7 mM). The cell bodies become elongated; distinct narrow processes are formed. With prolonged incubation, the cells show less tendency to pile up or become polygonal. Further, L-929 and Rous sarcomatransformed hamster cells orient in parallel arrays characteristic of contact inhibition. The cells retain their altered morphology as long as the butyryl-cyclic AMP is present, but revert after its removal. Experiments with cycloheximide, puromycin, and actinomycin D indicate that protein Synthesis, but not RNA synthesis, is required for the response. Microtubular proteins may be involved. No response is observed with normal fibroblasts or with various epithelial cells. The data suggest that cyclic AMP may be an important factor in the determination of morphology of normal fibroblasts and this function may be lost or altered during transformation.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ABERCROMBIE M., HEAYSMAN J. E. Observations on the social behaviour of cells in tissue culture. II. Monolayering of fibroblasts. Exp Cell Res. 1954 May;6(2):293–306. doi: 10.1016/0014-4827(54)90176-7. [DOI] [PubMed] [Google Scholar]
- Buckley I. K., Porter K. R. Cytoplasmic fibrils in living cultured cells. A light and electron microscope study. Protoplasma. 1967;64(4):349–380. doi: 10.1007/BF01666538. [DOI] [PubMed] [Google Scholar]
- Carter S. B. Effects of cytochalasins on mammalian cells. Nature. 1967 Jan 21;213(5073):261–264. doi: 10.1038/213261a0. [DOI] [PubMed] [Google Scholar]
- Goldman R. D., Follett E. A. The structure of the major cell processes of isolated BHK21 fibroblasts. Exp Cell Res. 1969 Oct;57(2):263–276. doi: 10.1016/0014-4827(69)90150-5. [DOI] [PubMed] [Google Scholar]
- Heidrick M. L., Ryan W. L. Cyclic nucleotides on cell growth in vitro. Cancer Res. 1970 Feb;30(2):376–378. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Robison G. A., Butcher R. W., Sutherland E. W. Cyclic AMP. Annu Rev Biochem. 1968;37:149–174. doi: 10.1146/annurev.bi.37.070168.001053. [DOI] [PubMed] [Google Scholar]
- Ryan W. L., Heidrick M. L. Inhibition of cell growth in vitro by adenosine 3',5'-monophosphate. Science. 1968 Dec 27;162(3861):1484–1485. doi: 10.1126/science.162.3861.1484. [DOI] [PubMed] [Google Scholar]
- STOKER M. REGULATION OF GROWTH AND ORIENTATION IN HAMSTER CELLS TRANSFORMED BY POLYOMA VIRUS. Virology. 1964 Oct;24:165–174. doi: 10.1016/0042-6822(64)90099-6. [DOI] [PubMed] [Google Scholar]
- SVOBODA J. Presence of chicken tumour virus in the sarcoma of the adult rat inoculated after birth with Rous sarcoma tissue. Nature. 1960 Jun 18;186:980–981. doi: 10.1038/186980b0. [DOI] [PubMed] [Google Scholar]
- Stoker M. G., Rubin H. Density dependent inhibition of cell growth in culture. Nature. 1967 Jul 8;215(5097):171–172. doi: 10.1038/215171a0. [DOI] [PubMed] [Google Scholar]