Abstract
The rate of multiplication of a population of cultured human lung fibroblasts is determined by the level of common nutrients and serum factors in the medium. By application of the principles of Henri--Michaelis--Menten kinetic analysis to cell growth in vitro, the relationship between the level of a macromolecular fraction of serum that contains growth factors and the concentration of individual nutrient that is required to support a half-maximal rate of cell multiplication was explored. The requirement for the majority of individual nutrients is independent of the level of serum factors in the medium. This includes all 20 amino acids, glucose, purines, pyrimidines, polyamines, choline, and inositol. In contrast, serum factors determine the cellular requirement for Ca2+, K+, Mg2+, Pi, and 2-oxocarboxylic acids. These nutrients are most likely involved in cellular processes related to the mechanism by which growth factors in serum control the cell multiplication rate.
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Selected References
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- Aharonov A., Passovoy D. S., Herschman H. R. Mitogenic response to epidermal growth factor: relationship to number, affinity, and down-regulation of EGF receptors in three murine embryo cell lines. J Supramol Struct. 1978;9(1):41–45. doi: 10.1002/jss.400090105. [DOI] [PubMed] [Google Scholar]
- Baker J. B., Simmer R. L., Glenn K. C., Cunningham D. D. Thrombin and epidermal growth factor become linked to cell surface receptors during mitogenic stimulation. Nature. 1979 Apr 19;278(5706):743–745. doi: 10.1038/278743a0. [DOI] [PubMed] [Google Scholar]
- Barsh G. S., Cunningham D. D. Nutrient uptake and control of animal cell proliferation. J Supramol Struct. 1977;7(1):61–77. doi: 10.1002/jss.400070107. [DOI] [PubMed] [Google Scholar]
- Bhargava P. M. Regulation of cell division and malignant transformation: a new model for control by uptake of nutrients. J Theor Biol. 1977 Sep 7;68(1):101–137. doi: 10.1016/0022-5193(77)90231-4. [DOI] [PubMed] [Google Scholar]
- Breenberg D. B., Barsh G. S., Ho T. S., Cunningham D. D. Serum-stimulated phosphate uptake and initiation of fibroblast proliferation. J Cell Physiol. 1977 Feb;90(2):193–210. doi: 10.1002/jcp.1040900206. [DOI] [PubMed] [Google Scholar]
- Brunette M. G., Vigneault N., Danan G. A new fluorometric method for determination of picomoles of inorganic phosphorus. application to the renal tubular fluid. Anal Biochem. 1978 May;86(1):229–237. doi: 10.1016/0003-2697(78)90338-x. [DOI] [PubMed] [Google Scholar]
- CONNERTY H. V., BRIGGS A. R., EATON E. H., Jr Simplified determination of the lipid components of blood serum. Clin Chem. 1961 Feb;7:37–53. [PubMed] [Google Scholar]
- Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham D. D., Pardee A. B. Transport changes rapidly initiated by serum addition to "contact inhibited" 3T3 cells. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1049–1056. doi: 10.1073/pnas.64.3.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Das M., Fox C. F. Molecular mechanism of mitogen action: processing of receptor induced by epidermal growth factor. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2644–2648. doi: 10.1073/pnas.75.6.2644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gospodarowicz D., Moran J. S. Growth factors in mammalian cell culture. Annu Rev Biochem. 1976;45:531–558. doi: 10.1146/annurev.bi.45.070176.002531. [DOI] [PubMed] [Google Scholar]
- HAKALA M. T., TAYLOR E. The ability of purine and thymine derivatives and of glycine to support the growth of mammalian cells in culture. J Biol Chem. 1959 Jan;234(1):126–128. [PubMed] [Google Scholar]
- Ham R. G., McKeehan W. L. Development of improved media and culture conditions for clonal growth of normal diploid cells. In Vitro. 1978 Jan;14(1):11–22. doi: 10.1007/BF02618170. [DOI] [PubMed] [Google Scholar]
- Ham R. G., McKeehan W. L. Media and growth requirements. Methods Enzymol. 1979;58:44–93. doi: 10.1016/s0076-6879(79)58126-9. [DOI] [PubMed] [Google Scholar]
- Holley R. W. A unifying hypothesis concerning the nature of malignant growth. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2840–2841. doi: 10.1073/pnas.69.10.2840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holley R. W. Control of growth of mammalian cells in cell culture. Nature. 1975 Dec 11;258(5535):487–490. doi: 10.1038/258487a0. [DOI] [PubMed] [Google Scholar]
- Kaplan J. G. Membrane cation transport and the control of proliferation of mammalian cells. Annu Rev Physiol. 1978;40:19–41. doi: 10.1146/annurev.ph.40.030178.000315. [DOI] [PubMed] [Google Scholar]
- Lechner J. F., Kaighn M. E. Application of the principles of enzyme kinetics to clonal growth rate assays: an approach for delineating interactions among growth promoting agents. J Cell Physiol. 1979 Sep;100(3):519–529. doi: 10.1002/jcp.1041000314. [DOI] [PubMed] [Google Scholar]
- McKeehan W. L., Genereux D. P., Ham R. G. Assay and partial purification of factors from serum that control multiplication of human diploid fibroblasts. Biochem Biophys Res Commun. 1978 Feb 28;80(4):1013–1021. doi: 10.1016/0006-291x(78)91346-3. [DOI] [PubMed] [Google Scholar]
- McKeehan W. L., Ham R. G. Calcium and magnesium ions and the regulation of multiplication in normal and transformed cells. Nature. 1978 Oct 26;275(5682):756–758. doi: 10.1038/275756a0. [DOI] [PubMed] [Google Scholar]
- McKeehan W. L., McKeehan K. A., Hammond S. L., Ham R. G. Improved medium for clonal growth of human diploid fibroblasts at low concentrations of serum protein. In Vitro. 1977 Jul;13(7):399–416. doi: 10.1007/BF02615100. [DOI] [PubMed] [Google Scholar]
- McKeehan W. L., McKeehan K. A. Oxocarboxylic acids, pyridine nucleotide-linked oxidoreductases and serum factors in regulation of cell proliferation. J Cell Physiol. 1979 Oct;101(1):9–16. doi: 10.1002/jcp.1041010103. [DOI] [PubMed] [Google Scholar]
- Megyesi K., Kahn C. R., Roth J., Neville D. M., Jr, Nissley S. P., Humbel R. E., Froesch E. R. The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. J Biol Chem. 1975 Dec 10;250(23):8990–8996. [PubMed] [Google Scholar]
- PARDEE A. B. CELL DIVISION AND A HYPOTHESIS OF CANCER. Natl Cancer Inst Monogr. 1964 May;14:7–20. [PubMed] [Google Scholar]
- Raizada M. K., Perdue J. F. Mitogen receptors in chick embryo fibroblasts. Kinetics, specificity, unmasking, and synthesis of 125I-insulin binding sites. J Biol Chem. 1976 Oct 25;251(20):6445–6455. [PubMed] [Google Scholar]
- Rubin H. Magnesium deprivation reproduces the coordinate effects of serum removal or cortisol addition on transport and metabolism in chick embryo fibroblasts. J Cell Physiol. 1976 Dec;89(4):613–625. doi: 10.1002/jcp.1040890418. [DOI] [PubMed] [Google Scholar]
- Sanui H., Rubin H. Correlated effects of external magnesium on cation content and DNA synthesis in culture chicken embryo fibroblasts. J Cell Physiol. 1977 Jul;92(1):23–31. doi: 10.1002/jcp.1040920104. [DOI] [PubMed] [Google Scholar]
- Schlessinger J., Shechter Y., Cuatrecasas P., Willingham M. C., Pastan I. Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5353–5357. doi: 10.1073/pnas.75.11.5353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tupper J. T., Del Rosso M., Hazelton B., Zorgniotti F. Serum-stimulated changes in calcium transport and distribution in mouse 3T3 cells and their modification by dibutyryl cyclic AMP. J Cell Physiol. 1978 Apr;95(1):71–84. doi: 10.1002/jcp.1040950110. [DOI] [PubMed] [Google Scholar]