Monte Carlo simulation of LNCaP human prostate cancer cell aggregation in liquid-overlay culture.
Neoplastic cells self-assemble in liquid-overlay cultures into multicellular spheroids that resemble micrometastases and avascular regions of larger tumors. A Monte Carlo simulation based on Meakin's cluster-cluster aggregation model resolved the physical mechanisms by which LNCaP human prostate cancer cells aggregate in this environment. The best-fit solution suggests that LNCaP cells aggregate with an adhesion probability of 0.5% when they migrate within a radius of influence between cell centers of 180 microm, 10 times the cell diameter. The sweeping radius of influence is indicative of cell tethering and/or chemotaxis and results in an intrinsic rate of self-aggregation that increases from k(11) = 1.5 h(-1) for single cells to k(1010) = 17.5 h(-1) for 10-mers. Similar rates are predicted by Smoluchowski's collision theory (1), suggesting that they are inherent properties of LNCaP liquid-overlay culture. Aggregates form more compact structures in culture than during simulation as measured by the fractal dimension: D(F) = 1.74 +/- 0.04 for 10-mers in culture vs D(F) = 1.25 +/- 0.10 for simulated 10-mers. Additional restructuring would further extend the radius of influence and diminish adhesion. Applications of this work include the production of highly viable spheroids for drug testing and basic oncological research.
Song
Hong
H
Chemical Engineering Department, Tulane University, New Orleans, Louisiana 70118, USA.
O'Connor
Kim C
KC
Lacks
Daniel J
DJ
Enmon
Richard M
RM
Jain
Shamik K
SK
D002448:Cell Adhesion; D002449:Cell Aggregation; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003198:Computer Simulation; D006801:Humans; D008297:Male; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012996:Solutions
D012996:Solutions