Short‐term rhythmic proliferation of human breast cancer cell lines: surface effects and fractal growth patterns

Journal of Pathology - Tập 197 Số 2 - Trang 163-169 - 2002
Roland Sedivy1, Stefan Thurner2,3, Alexandra C. Budinsky4, Wolfgang J. Köstler4, Christoph Zielinski4,5
1Clinical Department of Clinical Pathology, University of Vienna, Vienna, Austria
2Department of Otolaryngology, University of Vienna, Vienna, Austria
3Institute of Mathematics, University of Vienna, Vienna, Austria
4Clinical Division of Oncology, Department of Medicine I, University of Vienna, Vienna, Austria
5Ludwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria

Tóm tắt

AbstractKinetic studies of cell proliferation rates shed light on the growth dynamics of cancer. Most such studies are based on measurements of cell numbers that were evaluated in time intervals of about 12 h. Studies of the initial tumour growth with short measuring intervals are rare. This study was therefore designed with 1 h measuring intervals over a 24 h period. Human breast cancer cell lines (ZR‐75‐1, SK‐BR‐3, MCF‐7) and a benign cell line (HBL‐100) were used to study the hourly thymidine uptake as a measure of cells in synthesis. In parallel experiments, the same cell lines were also exposed to tumour necrosis factor alpha (TNF‐α) to explore the effect of an apoptosis‐inducing substance on initial tumour growth kinetics. In time‐evolution plots, there was an oscillation of the labelling index of thymidine uptake for all investigated cell lines, with and without TNF‐α. Based on the results obtained, a mathematical model was developed mimicking the real experiment. To describe the system dynamically a cellular automaton model was studied. The growth kinetics revealed by the simulation were in accordance with our experimental data. Two‐ and three‐dimensional growth simulations of this computer model yielded objects morphologically similar to real images of human breast cancer. Almost identical fractal dimensions of the virtual and real tumours further supported this visual similarity. The cellular automata models could, therefore, be seen as a bridge towards realistic in vivo scenarios. From a clinical point of view, the results obtained may be applicable not only to primary tumours, but even to tumour cell microfoci and small metastases, which are a major concern in early metastasizing tumours such as breast cancer. Copyright © 2002 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

Farber E, 1984, The multistep nature of cancer development, Cancer Res, 44, 4217

Rubin H, 1985, Cancer as a dynamic developmental disorder, Cancer Res, 45, 2935

10.1002/1097-0142(196804)21:4<600::AID-CNCR2820210409>3.0.CO;2-M

10.1038/bjc.1964.55

Goldie J, 1979, A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate, Cancer Treat Rep, 63, 1727

10.1073/pnas.18.1.1

Speer J, 1984, A stochastic numerical model of breast cancer that simulates clinical data, Cancer Res, 44, 4124

Norton LA, 1988, Gompertzian model of human breast cancer growth, Cancer Res, 48, 7067

10.1083/jcb.43.2.207

10.1242/jcs.86.1.191

10.1002/jss.400140307

10.1038/236019a0

10.1016/S0378-4371(98)00318-5

VoitikovaM.Cellular automaton for immunology of tumour growth.e‐print archive:1998; comp‐gas/9811001.

Tannock I, 1978, Cell kinetics and chemotherapy: a critical review, Cancer Treat Rep, 62, 1117

Sedivy R, 1996, Fractal tumours: their real and virtual images, Wien Klin Wochenschr, 108, 547

10.1016/0306-9877(90)90186-I

10.1002/jso.2930430312

10.1007/BF00666009

10.1023/A:1008263116022

10.1038/nm0295-149

10.1103/PhysRevLett.81.4008

10.1002/path.1711770115

10.1002/path.1711720406

10.1046/j.1365-2818.1997.1440701.x

10.1103/PhysRevLett.80.397

Posadas EM, 1996, Chaotic oscillations in cultured cells: rat prostate cancer, Cancer Res, 56, 3682

10.1182/blood.V87.12.5027.bloodjournal87125027

10.1002/(SICI)1096-9896(199606)179:2<210::AID-PATH560>3.0.CO;2-T

Baish JW, 2000, Fractals and cancer, Cancer Res, 60, 3683

10.1016/0046-8177(94)90294-1

10.1002/(SICI)1096-9896(199705)182:1<1::AID-PATH808>3.0.CO;2-B

Losa GA, 1996, Self‐similarity and fractal irregularity in pathologic tissues, Mod Pathol, 9, 174

10.1006/gyno.1999.5516

Thông tin
Thông tin xuất bản

Journal of Pathology

Tập 197 Số 2

163-169

Thông tin tác giả