Investigation of cellular movement in the prostate epithelium using an agent-based model.
Experimental patterns of epithelial cell proliferation in the prostate suggest that cell movement may play an important role in prostate epithelial homeostasis, and genes known to regulate cell movement are commonly mutated or deleted in prostate carcinomas. However, the nature of cell movement within the prostate epithelium remains unknown. Here, the role of cellular movement in the prostate epithelium was explored by developing an agent-based model of the prostate duct. Prostatic adult stem cells, transit amplifying/intermediate cells (TA/ICs), and luminal cells were individually modeled within a three-dimensional reconstruction of a prostate duct. Different movement behaviors for TA/ICs and luminal cells were assessed by their ability to recreate experimental patterns of prostate cell proliferation and epithelial morphology. Strongly directed TA/IC movement toward the distal region of the prostate duct combined with weakly directed luminal cell movement toward the proximal region of the prostate duct was able to best recreate experimental patterns of prostate proliferation and morphology. The effects on cell mobility from abnormalities in PTEN and thymosin beta15 (Tbeta15), genes which are commonly altered in prostate cancer, were simulated in the model. These simulations show that altering prostate stem cell movement can dysregulate epithelial homeostasis and lead to excessive cell growth, suggesting that disruption of cell movement may contribute to prostate carcinogenesis.
Lao
Bert J
BJ
Department of Bioengineering, University of California, 7523 Boelter Hall, Los Angeles, CA 90095, USA.
Kamei
Daniel T
DT
D000465:Algorithms; D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology; D051381:Rats; D013234:Stem Cells / Q000166:cytology; D013947:Thymosin / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016212:Transforming Growth Factor beta; C525161:thymosin beta15, rat; D013947:Thymosin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human