Abstract
In vivo-like drug responses are observed in three-dimensional culture but frequently not in two-dimensional culture, indicating that drug response may be a function of tissue architecture. Alexis Carrel introduced thatin vitro culture of tissues in the beginning of the century utilizing a culture system that allowed the three-dimensional growth of tissues. Leighton improved upon this system by developing a substrate of sponge matrices. Other methods of three-dimensional culture include collagen gels and what are known as organ culture systems on filters or meshes. In addition, cell suspensions can be converted into multicellular spheroids, another form of three-dimensional culture. Comparison of the three-dimensional culture methods with two-dimensional culture methods has shown critical differences in drug response. Thein vivo mechanism of drug resistance may involve alterations in cell-cell interaction which may occur in three-dimensional culture as opposed to monolayer culture.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Carrel A: On the permanent life of tissues outside the organism. J Exp Med 15: 516–528, 1912
Sherwin RP, Richters A, Yellin AE, Donovan AJ: Histoculture of human breast cancers. J Surg Oncol 13: 9–20, 1980
Leighton J: A sponge matrix method for tissue culture. Formation of organized aggregates of cellsin vitro. J Natl Cancer Inst 12: 545–561, 1951
Leighton J: The growth patterns of some transplantable animal tumors in sponge matrix tissue culture. J Natl Cancer Inst 15: 275–293, 1954
Leighton J, Justh G, Esper M, Kronenthal R: Collagen-coated cellulose sponge: three-dimensional matrix for tissue culture of Walker tumor 256. Science 155: 1259–1261, 1967
Leighton J: Aggregate replication, a factor in the growth of cancer. Science 129: 466–467, 1959
Leighton J: The propagation of aggregates of cancer cells: implications for therapy and a simple method of study. Cancer Chemother Rep 9: 71–72, 1960
Leighton J, Kalla RL, Turner JM, Fennell RH: Pathogenesis of tumor invasion. II. Aggregate replication. Cancer Res 20: 575–586, 1960
Leighton J, Kalla RL, Kline 1, Belkin M: Pathogenesis of tumor invasion. 1. Interactions between normal tissues and ‘transformed’ cells in tissue culture. Cancer Res 19: 23–27, 1959
Leighton J, Siar JW, Mahoney MJ: Examination of invasion by manipulating stroma and parenchyma of carcinomasin vitro andin vivo. In: Brennan MJ, Simpson EL (eds) Biological Interactions in Normal and Neoplastic Growth: A Contribution to the Host-Tumor Problem. Boston: Little, Brown and Company 1962: 681–702
Leighton J: Structural biology of epithelial tissue in histophysiologic gradient culture.In vitro Cell Dev Biol 28A: 482–492, 1992
Yang J, Richards J, Bowman PD, Guzman R, Enami J, McCormick K, Hamamoto S, Pitelka D, Nandi S: Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels. Proc Natl Acad Sci USA 76: 3401–3405, 1979
Strangeways TSP: Tissue Culture in Relation to Growth and Differentiation. Cambridge, England: W Heffer and Sons Ltd, 1924
Fell HB, Robinson R: The growth, development and phosphatase activity of embryonic avian femora and end-buds cultivatedin vitro. Biochem J 23: 767–784, 1929
Browning TH, Trier JS: Organ culture of mucosal biopsies of human small intestine. 48: 1423–1432, 1969
Inch WR, McCredie JA, Sutherland RM: Growth of nodular carcinomas in rodents compared with multi-cell spheroids in tissue culture. Growth 34: 271–282, 1970
Li LH, Bhuyan BK, Wallace TL: Comparison of cytotoxicity of agents on monolayer and spheroid systems. Proc Am Assoc Cancer Res 30: 2435a, 1989
Smith KS, Badiner GJ, Adams FG, Wilson DK, Li LH, Bhuyan BK: Modified 2-tumor (L1210, colon 38) assay to screen for solid tumor selective agents. In: Proceedings of the Symposium on Anticancer Drug Discovery and Development. Detroit: (in press)
Hoffman RM: Three-dimensional histoculture: origins and applications in cancer research. Cancer Cells 3: 86–92, 1991
Lawler EM, Miller FR, Heppner GH: Significance of three-dimensional growth patterns of mammary tissues in collagen gels.In Vitro 19: 600–610, 1983
Miller BE, Miller FR, Heppner GH: Assessing tumor drug sensitivity by a newin vitro assay which preserves tumor heterogeneity and subpopulation interactions. J Cell Physiol 3 (suppl): 105–116, 1984
Miller BE, Miller FR, Heppner GH: Factors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures. Cancer Res 45: 4200–4205, 1985
Teicher BA, Herman TS, Holden SA, Wang YY, Pfeffer MR, Crawtord JW: Tumor resistance to alkylating agents conferred by mechanisms operative onlyin vivo. Science 247: 1457–1461, 1990
Olive PL, Durand RE: Effect of intercellular contact on DNA conformation, radiation-induced DNA damage, and mutation in Chinese hamster V79 cells. Radiation Res 101: 94–101, 1985
Kobayashi H, Man S, Graham CH, Kapitain SJ, Teicher BA, Kerbel RS: Acquired multicellularmediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA 90: 3294–3298, 1993
Kawai K, Kamatani N, Georges E, Ling V: Identification of a membrane glycoprotein overexpressed in murine lymphoma sublines resistant to cis-diamine dichloroplatinum (II). J Biol Chem 265: 13,137–13,142, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hoffman, R.M. The three-dimensional question: can clinically relevant tumor drug resistance be measuredin vitro?. Cancer Metast Rev 13, 169–173 (1994). https://doi.org/10.1007/BF00689634
Issue Date:
DOI: https://doi.org/10.1007/BF00689634