Tuesday, March 14, 2017

Stochastic model of contact inhibition and the proliferation of melanoma in situ

Stochastic model of contact inhibition and the proliferation of melanoma in situ

Mauro Cesar C MoraisIzabella StuhlAlan U SabinoWillian W LautenschlagerAlexandre S QueirogaTharcisio C TortelliRoger ChammasYuri SuhovAlexandre F Ramos


Contact inhibition is a central feature orchestrating cell proliferation in culture experiments with its loss being associated with malignant transformation and tumorigenesis. We performed a co-culture experiment with human metastatic melanoma cell line (SK-MEL-147) and immortalized keratinocyte cells (HaCaT). After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. In addition, we observed that the proportion of melanoma cells within the total population has increased. To explain our results we propose a spatial stochastic model (following a philosophy of the Widom-Rowlinson model from Statistical Physics and Molecular Chemistry) where we consider cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. Our numerical simulations demonstrate that loss of contact inhibition is a sufficient mechanism, appropriate for an explanation of the increase in the proportion of tumor cells and generation of spatial patterns established in conducted experiments.