Protective effect of Heparins

H. SchillersSince cancer patients show an increased risk of venous thromboembolism, anticoagulant treatment with vitamin K antagonists or heparins is customary. A meta-analysis of clinical trials of the past 20 years showed an improved survival in cancer patients treated with heparin. This effect of heparin is based on mechanisms that are different from its antithrombotic effect and linked to the ability of influencing directly the tumor biology. Tumor cells in blood stream adhere to platelets and this adhesion is probably mediated by platelet surface molecules like GPIIb/IIIa, GPIb and P-selectin. Heparin blocks P-Selectin and this might be responsible for reduced malignancy by inhibiting the initial step of platelet-tumor cell interaction. However the interacting receptors and adhesion molecules remain to be elucidated.
Binding of platelets to tumor cells is a crucial step for the malignancy of cancer. Therefore, insights into this process may contribute to the optimization of tumor therapies.
We use optical imaging methods and single-cell force spectroscopy (SCFS) to investigate and to quantify the interaction of human non-small lung cancer cells (A549) with platelets. A focus in this project is to quantify the inhibitory effect of different types of heparins and to identify interacting receptors and adhesion molecules.

  • Single-cell force spectroscopy (SCFS)

    Scheme of single cell force spectroscopy (SCFS) (A) and a resulting force-distance curves (B). Human non-small lung cancer cells (A549) were glued with WGA to tipless cantilevers. This `cell-probe´ approaches to platelets on a collagen I coated surface (I) untill a force of 2 nN is reached (II). The cell probe is retracted and the cantilever bends because of the adhesive strength between the cell and the platelet and the cell starts to detach (III). The force detected at this point corresponds to the maximum adhesion/detachment force (FD). During further retraction of the cantilever, the contact area between cell and substrate shrinks and the cell sequentially detaches from the platelet (III) until cell and platelet are completely separated (IV). The shaded area in B represents the measured work of cell detachment (WD) from the substrate.