Origins and evolution of cell phenotypes in breast tumors.
This study presents a stochastic model that correlates genomic instability with tumor formation. The model describes the time- and space-variant volumetric concentrations of cancer cells of various phenotypes in a breast tumor. The cells of epithelial origin in the cancerous breast tissue are classified into four different phenotypes, normal epithelial cells and the grade 1, grade 2 and grade 3 cancer cell types with increasing potential for growth and invasion. Equations governing the time course of volumetric concentrations of cell phenotypes are derived by using the principle of conservation of mass. Cell migration into and from the stroma is taken into account. The transformations between cell phenotypes are due to genetic inheritance and chromosome aberrations. These transformations are assumed to be stochastic functions of the local cell concentration. The simulations of the model for planar geometry replicate the shapes of human breast tumors and capture the time history of tumor growth in animal models. Simulations point to transformation of tumor cell population from heterogeneous compositions to a single phenotype at advanced stages of invasive tumors. Systematic variations of model parameters in the computations indicate the important roles the migration capacity, proliferation rate, and phenotype transition probability play in tumor growth. The model developed provides realistic simulations for standard breast cancer therapies and can be used in the optimization studies of chemotherapy, radiotherapy, hormone therapy and emerging individualized therapies for cancer.
Tözeren
Aydin
A
School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA. aydin.tozeren@drexel.edu
Coward
Charles W
CW
Petushi
Sokol P
SP
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D002455:Cell Division; D003198:Computer Simulation; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D023421:Models, Animal; D008957:Models, Genetic; D010641:Phenotype