MPI for Heart and Lung Research
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Project leader: Dr. Boris Strilic

PhD Students: Lida Yang, Joseph Sayali

Technical Assistant: Dagmar Magalei

figure Platelet-mediated tumor cell extravasation

Processes underlying tumor cell extravasation. Tumor cells extravasate by transendothelial migration, which is a complex process involving various cell types and mechanisms. APP expressed by tumor cells can induce endothelial necroptosis through activation of death receptor 6 (DR6). Endothelial cell necroptosis may lead to gaps in the endothelial layer allowing tumor cells to extravasate. Alternatively, necroptotic endothelial cells release damage-associated molecular pattern (DAMPs) molecules, such as ATP, which act on adjacent cells to induce via specific receptors (such as P2Y2 receptors) specific signal transduction processes which result in an opening of the endothelial barrier allowing tumor cells to extravasate. The latter process is facilitated by tumor cell-activated platelets which, after activation, release ATP and further promote opening of the endothelial barrier. For details see Schumacher et al., 2013 and Strilic et al., 2016.

The goal of this novel research area is to better understand the mechanisms underlying tumor cell transendothelial migration during metastasis. Using in vitro and in vivo models we were able to identify the mechanism underlying the long-known prometastastic effect of platelets which facilitate tumor cell extravasation by promoting the opening of the endothelial barrier in a tumor cell dependent manner (Schumacher/Strilić et al, 2013). In addition we have recently shown that tumor cell-induced endothelial necroptosis is required for efficient tumor cell extravasation and metastasis (Strilic et al., 2016).

Literature

Strilic B, Yang L, Albarrán-Juárez J, Wachsmuth L, Han K, Müller UC, Pasparakis M, Offermanns S (2016). Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis. Nature 536, 215-8

Schuhmacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S (2013). Platelet-derived nucleoides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 24, 130-137