Tumor cells and platelets are known to form an unholy alliance increasing cancer progression in numerous ways. After extravasation into circulation a cancer cell is subjected to immune surveillance and natural killer cell-mediated cytolysis. Furthermore, shear force caused by the blood stream reduces the chance of extravasation. Cancer cell-induced platelet activation is a trick of cancer cells to “hijack” the services of host cells. Activated platelets bind to cancer cells and form a protective cloak which helps them to escape the immune system. Platelet adhesion to cancer cells facilitates tethering and arrest of disseminated cancer cells in the vasculature, enhances invasive potentials and thus extravasation of cancer cells. However, the exact mechanisms how platelets influence blood-borne metastasis remain poorly understood. Tumor cells adhere to the circulating platelets and this adhesion was probably mediated by such platelet surface molecules as GPIIb/IIIa, GPIb and P-selectin.However, so far the adhesion molecules mediating the platelet-tumor cell interaction are poorly characterized.
Platelet-tumor cell interaction
Up to now it was shown that the platelet-tumor cell contact prime tumor cells for subsequent metastasis2 and that platelet-derived microvesicles (PDM) (also known as platelet-derived microparticles (PDMP) are able to fuse with cells 3. There is also evidence of a fusion of platelets with endothelial cells 4. It remains unclear how tumor cells “hijack” the services of platelets.
We use optical imaging methods and atomic force microscopy (AFM) techniques to investigate the interaction of human non-small lung cancer cells (A549) with platelets. A focus in this project is to follow the interaction after initial adehesion in order to clarify the underlying mechanisms.
- Helenius J, Heisenberg CP, Gaub HE, Muller DJ. Single-cell force spectroscopy. J Cell Sci. 2008;121:1785-1791.
- Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 2011;20:576-590.
- Janowska-Wieczorek A, Wysoczynski M, Kijowski J et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int.J Cancer 2005;113:752-760.
- Zhang N, Zhang WJ, Cai HQ et al. Platelet adhesion and fusion to endothelial cell facilitate the metastasis of tumor cell in hypoxia-reoxygenation condition. Clin.Exp.Metastasis 2011;28:1-12.
3D view of one platelet beside and three platelets on a A549 cell (A) Hi-res AFM image gave the impression that platelets fuse with plasma membrane of A549 cells. Image was taken using peak-force tapping mode on a Catalyst (Bruker, Santa Barbara /USA).
Quantitative nanomechanical mapping of a living platelet. Data channel visualize submembraneous vesicles in an activated platelet. Data were taken using peak-force QNM on a Resolve (Bruker, Santa Barbara /USA).