Abstract B71: Stochastic model of contact inhibition and the proliferation of melanoma in situ

Abstract

Abstract Contact inhibition of proliferation can be described as the decrease of proliferation rates when the cell density increases. Its loss is a key feature of tumor development. Cell density of human metastatic melanoma cell line (SK-MEL-147) and immortalized keratinocyte cells (HaCaT) was evaluated daily in culture experiments. Keratinocytes reach lower cell density than melanoma cells at confluence, indicating that the population growth arrest is associated with contact inhibition (KHaCaT = 1779.6 ± 130.5 cells/mm2; KSK-MEL-147 = 5043.5 ± 316.5 cells/mm2). We performed a coculture experiment to assess the proliferation restriction between both cell lines. After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. Despite showing approximately the same proliferation rates when data were fitted with a logistic model (ρHaCaT = 1.1 ± 0.1 days-1; ρSK-MEL-147 = 1.1 ± 0.3 days-1), the proportion of melanoma cells within the total population has increased from 1:10 to 1:4 approximately. To explain our results we propose a spatial stochastic model where we consider cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. The agreement between experimental results and numerical simulation indicates that loss of contact inhibition is important for the analysis of the development of melanoma in situ, and explains the increase in the proportion of tumor cells and generation of spatial patterns established in conducted experiments. In addition, the distribution of the distances between cells of the same line indicates the higher proximity of melanoma cells and allowed us to identify their clustering pattern. This work provides results of a quantitative study of the impact of contact inhibition upon formation and growth of tumor-like melanoma cell clusters in a coculture with keratinocytes. Citation Format: Mauro Cesar C. Morais, Izabella Stuhl, Alan U. Sabino, Willian W. Lautenschlager, Alexandre S. Queiroga, Tharcisio C. Tortelli, Jr., Roger Chammas, Yuri Suhov, Alexandre F. Ramos. Stochastic model of contact inhibition and the proliferation of melanoma in situ [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B71.