October 2010 - New funding for anti-cancer studies at the IBL
A consortium of researchers from the Leiden University Medical Center (LUMC), the Leiden Institute of Physics (LION) and the Institute of Biology Leiden (IBL) received an interdisciplinary TOP GO grant for fundamental studies with potential for novel cancer treatments.
Prof. Dr. Pancras Hogendoorn (LUMC), Dr. Annemarie Meijer (IBL), Prof. Dr. Thomas Schmidt (LION) and Dr. Ewa Snaar-Jagalska (IBL) received an interdisciplinary TOP GO grant for a project based on angiogenesis inhibition and cellular immunotherapy. The integrative project with components at clinical, biological and biophysical level is entitled: ”The role of chemokine gradient sensing in Ewing’s sarcoma progression, angiogenesis and immune targeting”.
Ewing’s sarcoma is a malignant bone tumor most commonly found in children and young adults. The genetic abnormality causing Ewing’s sarcoma is known as a consistent reciprocal chromosomal translocation, but with current therapies the survival rates are only 60-65% in the case of early diagnosis. Patients with metastases have very poor prognosis.
The interaction of Ewing’s sarcoma cells with the tumor microenvironment is essential for tumor growth, angiogenesis and metastasis. The role of chemokines therein is ambivalent. Chemokines secreted by tumor cells attract immune cells, particularly leukocytes to tumor sites to increase tumor growth, while other immune cells may enhance anti-tumor immunity. Chemokines can also indirectly affect tumor growth by their angiogenic and angiostatic activity. Angiogenesis, the formation of new blood vessels from established ones is required to deliver nutrients and oxygen and to remove waste products from the cancer cells. Tumor growth occurs when the equilibrium between angiogenic and angiostatic factors is disturbed in favor of the angiogenic factors.
Both functions of chemokines make them potential therapeutic targets for immunotherapy and anti-angiogenesis treatment. In order to design a new therapeutic strategy there is, however, a clear need to generate more fundamental knowledge of the chemokine network underlying Ewing’s sarcoma disease. Currently, little is known about the specificity of chemokines that are secreted by Ewing’s sarcoma cells and that trigger directional cell migration of leucocytes and endothelial cells. Also the molecular/cell-biological mechanisms that control chemokine gradient sensing and migration of immune, endothelial and tumor cells are largely unknown.
- Cancer cells
Spreading of red-labeled cancer cells in a zebrafish (Danio rerio)
The Leiden consortium with researchers from LUMC, LION, and IBL combines expertise in various aspects of the pathology of Ewing’s sarcoma, including extensive experience with studies in zebrafish. The project will focus on very detailed molecular descriptions combined with results of this in vivo model system, which closely resembles the human situation. Due to the availability of large sets of human tumors, sera, and patient lymphocytes the correlates can be translated to the human situation.