Growth in solid heterogeneous human colon adenocarcinomas: comparison of simple logistical models

Abstract. Three models of simple logistical growth were used to describe volumetric growth in heterogeneous tumours. Two clonal subpopulations (designated as clone A and clone D) originally obtained from a human colon adenocarcinoma were used to produce solid xenograft tumours in nude mice. Volumetric growth of tumours produced from pure cells alone was compared to that produced from 50% A:50% D, 88% A:12% D, and 9% A:91% D admixtures. Gompertzian analysis of the in vivo growth data indicated significant differences in both the initial growth rates and final asymptotic limiting volumes of the pure versus the admixed tumours. Verhulstian and modified Verhulstian models were also used to derive regression curves from the same data. The fit of the curves was compared with each other using standard (Akaike, 1974; Schwartz, 1978) information criteria. In four of the five tumour populations the Gompertz equation fitted best. Only in the 88% A:12% D tumours did the modified Verhulst model fit best. The deviations from the regression curves, the residuals, for all three models were systematically distributed. These systematic errors are likely to be the result of using simplified logistical models to describe the growth kinetics of interacting populations in heterogeneous tumours.

[1]  J. Leith,et al.  Growth properties of artificial heterogeneous human colon tumors. , 1987, Cancer research.

[2]  G. Schwarz Estimating the Dimension of a Model , 1978 .

[3]  I. N. Katz,et al.  Stochastic processes for solid tumor kinetics II. Diffusion-regulated growth , 1974 .

[4]  D. Dexter,et al.  Enhancement of the responses of human colon adenocarcinoma cells to X-irradiation and cis-platinum by N-methylformamide (NMF). , 1985, International journal of radiation oncology, biology, physics.

[5]  I. Tannock,et al.  Influence of glucose concentration on growth and formation of necrosis in spheroids derived from a human bladder cancer cell line. , 1986, Cancer research.

[6]  D. Dexter,et al.  Heterogeneity of cancer cells from a single human colon carcinoma. , 1981, The American journal of medicine.

[7]  D. Dexter,et al.  Tumor heterogeneity and drug resistance. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  J. Leith,et al.  Enhancement of radiation injury in human colon tumor cells by the maturational agent sodium butyrate (NaB). , 1985, Radiation research.

[9]  G. Heppner Tumor heterogeneity. , 1984, Cancer research.

[10]  D. Dexter,et al.  Human tumor cell heterogeneity and metastasis. , 1983, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  G. Poste CELLULAR HETEROGENEITY IN MALIGNANT NEOPLASMS AND THE THERAPY OF METASTASES , 1982, Annals of the New York Academy of Sciences.

[12]  J. Freyer,et al.  Regulation of growth saturation and development of necrosis in EMT6/Ro multicellular spheroids by the glucose and oxygen supply. , 1986, Cancer research.

[13]  J. Dewyngaert,et al.  Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro. , 1982, Cancer research.

[14]  W. Kendal,et al.  Gompertzian growth as a consequence of tumor heterogeneity , 1985 .

[15]  J. Leith,et al.  Tumor micro-ecology and competitive interactions. , 1987, Journal of theoretical biology.

[16]  I. N. Katz,et al.  Stochastic processes for solid tumor kinetics I. surface-regulated growth☆ , 1974 .

[17]  I. Fidler,et al.  Tumor heterogeneity and the biology of cancer invasion and metastasis. , 1978, Cancer research.

[18]  P. Waltman Competition models in population biology , 1983 .

[19]  F. Miller,et al.  Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor. , 1980, Cancer research.

[20]  J. Leith,et al.  Effects of nutritional state on the expression of radiation injury in two tumor subpopulations obtained from a heterogeneous human colon carcinoma. , 1986, International journal of radiation oncology, biology, physics.

[21]  I. Tannock,et al.  Influence of hypoxia and an acidic environment on the metabolism and viability of cultured cells: potential implications for cell death in tumors. , 1986, Cancer research.

[22]  H. Akaike A new look at the statistical model identification , 1974 .

[23]  J P Freyer,et al.  Proliferative and clonogenic heterogeneity of cells from EMT6/Ro multicellular spheroids induced by the glucose and oxygen supply. , 1986, Cancer research.

[24]  O. Alabaster TUMOR CELL METABOLIC HETEROGENEITY: THE ROLE OF METABOLIC MODIFICATION IN CHEMOTHERAPY , 1982 .

[25]  D. Dexter,et al.  Disaggregation studies of xenograft solid tumors grown from pure or admixed clonal subpopulations from a heterogeneous human colon adenocarcinoma. , 1985, Invasion & metastasis.