Abstract
Three-dimensional growth of tumour cells facilitates direct and close-range cell-cell interactions which may modify cellular metabolism, proliferation and differentiation, as well as sensitivity to cytotoxic chemicals and physical agents. The development of procedures for growing human tumours in three dimensions under well-defined experimental conditions has therefore allowed for new types of biological and physiological studies not feasible with monolayer cell cultures. Two three-dimensional models for human cancer, multicellular spheroids and xenografted tumours, are described and discussed in this chapter.
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References
Bruland, Ø., Fodstad, Ø. and Pihl, A. (1985). The use of multicellular spheroids in establishing human sarcoma cell lines in vitro. Int. J. Cancer 35:793–798.
Carlsson, J. and Acker, H. (1988). Relations between pH, oxygen partial pressure and growth in cultured cell spheroids. Int. J. Cancer 42:715–720.
Carlsson, J. and Nederman, T. (1989). Tumour spheroid technology in cancer therapy research. Eur. J. Cancer Clin. Oncol. 25:1127–1133.
Carlsson, J., Nilsson, K., Westermark, B., Pontén, J., Sundström, C., Larsson, E., Bergh, J., Påhlman, S., Busch, C. and Collins, V.P. (1983). Formation and growth of multicellular spheroids of human origin. Int. J. Cancer 31:523–533.
Dertinger, H., Guichard, M. and Malaise, E.P. (1984). Relationship between intercellular communication and radiosensitivity of human tumor xenografts. Eur. J. Cancer Clin. Oncol. 20:561–566.
Fidler, I.J. (1986). Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Met. Rev. 5:29–49.
Giovanella, B.C. and Fogh, J. (1985). The nude mouse in cancer research. Adv. Cancer Res. 44:69–120.
Glimelius, B., Norling, B., Nederman, T. and Carlsson, J. (1988). Extracellular matrices in multicellular spheroids of human glioma origin. Increased incorporation of proteoglycans and fibronectin as compared to monolayer cultures. Acta Pathol. 96:433–444.
Haji-Karim, M. and Carlsson, J. (1978). Proliferation and viability in cellular spheroids of human origin. Cancer Res. 38:1457–1464.
Houghton, J.A. and Taylor, D.M. (1978). Growth characteristics of human colorectal tumours during serial passage in immune-deprived mice. Br. J. Cancer 37:213–223.
Inch, W.R., McCredie, J.A. and Sutherland, R.M. (1970). Growth of nodular carcinomas in rodents compared with multi-cell spheroids in tissue culture. Growth 34:271–282.
Kallinowski, F., Vaupel, P., Runkel, S., Berg, G., Fortmeyer, H.P., Baessler, K.H., Wagner, K., Mueller-Klieser, W. and Walenta, S. (1988). Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distributions in human breast cancer xenografts in nude rats. Cancer Res. 48:7264–7272.
Mattern, J., Wayss, K., Haag, D., Toomes, H. and Volm, M. (1980). Different growth rates of lung tumours in man and their xenografts in nude mice. Eur. J. Cancer 16:289–291.
Mueller-Klieser, W. (1987). Multicellular spheroids. A review on cellular aggregates in cancer research. J. Cancer Res. Clin. Oncol. 113:101–122.
Mueller-Klieser, W., Freyer, J.P. and Sutherland, R.M. (1986). Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids. Br. J. Cancer 53:345–353.
Nederman, T., Norling, B., Glimelius, B., Carlsson, J. and Brunk, U. (1984). Demonstration of an extracellular matrix in multicellular tumor spheroids. Cancer Res. 44:3090–3097.
Rofstad, E.K. (1985). Human tumour xenografts in radiotherapeutic research. Radiother. Oncol. 3:35–46.
Rofstad, E.K. (1986). Growth and radiosensitivity of malignant melanoma multicellular spheroids initiated directly from surgical specimens of tumours in man. Br. J. Cancer 54:569–578.
Rofstad, E.K. (1989). Local tumor control following single dose irradiation of human melanoma xenografts: Relationship to cellular radiosensitivity and influence of an immune response by the athymic mouse. Cancer Res. 49:3163–3167.
Rofstad, E.K., DeMuth, P., Fenton, B.M. and Sutherland, R.M. (1988a). 31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia. Cancer Res. 48:5440–5446.
Rofstad, E.K., Fenton, B.M. and Sutherland, R.M. (1988b). Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: Relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Br. J. Cancer 57:494–502.
Rofstad, E.K., Fodstad, Ø. and Lindmo, T. (1982). Growth characteristics of human melanoma xenografts. Cell Tissue Kinet. 15:545–554.
Rofstad, E.K. and Sutherland, R.M. (1989). Growth and radiation sensitivity of the MLS human ovarian carcinoma cell line grown as multicellular spheroids and xenografted tumours. Br. J. Cancer 59:28–35.
Rofstad, E.K., Wahl, A., Davies, C. de L and Brustad, T. (1986). Growth characteristics of human melanoma multicellular spheroids in liquid-overlay culture: Comparisons with the parent tumour xenografts. Cell Tissue Kinet. 19:205–216.
Rygaard, J., Brünner, N., Græm, N. and Spang-Thomsen, M. (1987). Immune-Deficient Animals in Biomedical Research. S Karger AG, Basel.
Sharkey, F.E. and Fogh, J. (1984). Considerations in the use of nude mice for cancer research. Cancer Met. Rev. 3:341–360.
Solesvik, O.V., Rofstad, E.K. and Brustad, T. (1982). Vascular structure of five human malignant melanomas grown in athymic nude mice. Br. J. Cancer 46:557–567.
Steel, G.G. (1978). The growth and therapeutic response of human tumours in immune deficient mice. Bull. Cancer 65:465–472.
Steel G.G. and Peckham M.J. 1980. Human tumour xegrafts A critical appraisal. Br. J. Cancer 41 Suppl. IV133–141
Sutherland, R.M. (1988). Cell and environment interactions in tumor microregions: The multicell spheroid model. Science 240:177–184.
Sutherland, R.M. and Durand, R.E. (1976). Radiation effects on mammalian cells grown as an in vitro tumor model. Curr. Top. Radiat. Res. 11:87–139.
Sutherland, R.M., McCredie, J.A. and Inch, W.R. (1971). Growth of multicellular spheroids in tissue culture as a model of nodular carcinomas. J. Natl. Cancer Inst. 46:113–120.
Sutherland, R.M., Rasey, J.S. and Hill, R.P. (1988). Tumor biology. Am. J. Clin. Oncol. 11:253–274.
Sutherland, R.M., Sordat, B., Bamat, J., Gabbert, H., Bourrat, B. and Mueller-Klieser, W. (1986). Oxygenation and differentiation in multicell spheroids of human colon carcinoma. Cancer Res. 46:5320–5329.
Vaupel, P., Fortmeyer, H.P., Runkel, S. and Kallinowski, F. (1987). Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res. 47:3496–3503.
West, C.M.L. and Sutherland, R.M. (1987). The radiation response of a human colon adenocarcinoma grown in monolayer, as spheroids, and in nude mice. Radiat. Res. 112:105–115.
Wibe, E., Berg, J.P., Tveit, K.M., Nesland, J.M. and Lunde, S. (1984). Multicellular spheroids grown directly from human tumour material. Int. J. Cancer 34:21–26.
Yuhas, J.M., Li, A.P., Martinez, A.O. and Ladman, A.J. (1977). A simplified method for production and growth of multicellular tumor spheroids. Cancer Res. 37:3639–3643.
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Rofstad, E.K. (1991). Spheroids and Xenografts. In: Masters, J.R.W. (eds) Human Cancer in Primary Culture, A Handbook. Developments in Oncology, vol 64. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3304-3_4
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DOI: https://doi.org/10.1007/978-94-011-3304-3_4
Publisher Name: Springer, Dordrecht
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