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How cancer reprograms megakaryocytes and platelets

Confocal image of bone marrow in breast cancer, depicting megakaryocytes (cyan) and blood vessels (magenta). Image taken by Dr. Isabelle Becker.

Platelets are produced by megakaryocytes that predominantly reside within the bone marrow. We aim to determine whether malignancy influences megakaryocyte maturation and platelet production within the bone marrow milieu. We believe that megakaryocytes in the setting of cancer are reprogrammed and undergo abnormal thrombopoiesis, producing platelets that look fundamentally different to those made in healthy individuals.

Crosstalk Between Platelets and Tumor Cells

We aim to understand the molecular crosstalk that occurs between platelets and tumor cells to determine 1) how platelets become activated in response to tumor cells and 2) how interaction with platelets regulates the metastatic phenotype of tumor cells. Specifically, we are interested the immune regulatory function of platelets to tumor cells. We found that platelet upregulate tumor cell PD-L1 level in EGFR dependent way. Given the recent clinical trials establishing that anti-platelet agents such as aspirin can improve survival and decrease metastatic spread in some cancer patients, we also aim to understand how anti-platelet therapies disrupt the effects of platelet to tumor cells.

Confocal image of a tumor cell (red) interacting with platelets (green).

Granular organization in megakaryocytes and platelets

Immunofluorescent staining of alpha granules within a megakaryocyte.

Early studies in our laboratory established that platelets differential package and secrete pro- and anti-angiogenic factors such that platelets can direct the angiogenic and metastatic response. We now aim to understand further how these factors are preferentially endocytosed by megakaryocytes and platelets and how this is influenced by anti-platelet therapies.

The Roles of Antiplatelet Drugs on Endocytosis

Platelets are known to endocytose a variety of factors while in circulation. Affectionately referred to as our “Sponge Project,” our goal of this research is to expand on the known library of molecules that platelets take up. Here we identify novel targets of platelet uptake, including both pro and anti-angiogenic factors. By determining the mechanism of uptake, we aim to identify molecular targets for therapeutic modulation of platelet endocytosis to aid in the formation or disruption of neo-angiogenesis in clinical pathologies.

Megakaryocytes loaded with transferrin that becomes fluorescent upon internalization.

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