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Förslaget inkom 2010-09-16

Does the cannabinoid receptor ligand hemopressin induce cell death in lymphoma?

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
Introduction:
Mantle cell lymphoma is a type of Non-Hodgkin B cell lymphoma comprising approximately 8% of malignant lymphomas. It has one of the worst prognoses of lymphomas with a median survival of 3-5 years and therefore new therapies are needed. The initiating event in the molecular pathogenesis of MCL is a translocation (11;14), which results in the overexpression of protein called cyclin D1, which participates in regulation of cell cycle. However, other genetic aberrations than t(11;14) also occur. We have previously found that cannabinoid receptors CB1 and CB2 are highly expressed in MCL and that activating them causes cell death of malignant but not normal B cells.
Most ligands to CB receptors are lipids or synthetic potent agonists. Hemopressin is so far the only identified peptide with affinity to CB1. Hemopressin is a 9 amino acid peptide derived from alpha-hemoglobin, the main constituent of red blood cells.

Aim:
This study aims to evaluate the effect of hemopressin on the viability of MCL and normal B cells. The student will also investigate cannabinoid-induced pathways leading to growth arrest or cell death of lymphoma cells.

Materials and Methods:
MCL cell lines and cell lines derived from normal B lymphocytes
Tumor cells and normal B lymphocytes isolated from patients
Cell culture
Cell viability assay based on spectrophotometric readout (XTT)
Western blotting (including sample preparation and electrophoresis)

Importance:
This project will provide important new knowledge on the role of cannabinoid receptors and cannabinoids in the pathogenesis of MCL and might have clinical implications.


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