Introduction to antibodies
An antibody is essentially a protein generated by the immune system in response to the detection of antigens in the body.
The video below explains the role of antibodies in the immune response.
The video below explains the role of antibodies in the immune response.
Hallmarks of cancer
Cancer is defined as the process by which the cells in the body become abnormal and proliferate out of control as a result of mutations in their genes.
These abnormal cells may form a malignant tumour which essentially invades adjacent regions and can spread to other areas in the body. This is called metastasis, whereby cells are able to travel to other areas in the body via the blood stream or lymphatic system.
Cancer can be caused by internal (e.g. inherited mutations) and external factors (e.g. chemicals, radiation) however it is important to note that ALL cancers arise due to mutations in the genes which control cell growth and division.
The figure below depicts the distinct features cancer cells exhibit in contrast to healthy cells. A hallmark of interest for this study is "Avoiding immune destruction".
These abnormal cells may form a malignant tumour which essentially invades adjacent regions and can spread to other areas in the body. This is called metastasis, whereby cells are able to travel to other areas in the body via the blood stream or lymphatic system.
Cancer can be caused by internal (e.g. inherited mutations) and external factors (e.g. chemicals, radiation) however it is important to note that ALL cancers arise due to mutations in the genes which control cell growth and division.
The figure below depicts the distinct features cancer cells exhibit in contrast to healthy cells. A hallmark of interest for this study is "Avoiding immune destruction".
CD47-SIRP alpha Interaction
The ratio between “eat me” and “don’t eat me” signals control the phagocytic fate of cells.
SIRPα is a transmembrane protein consisting of three extracellular domains and two cytoplasmic tyrosine phosphorylation sites (Takada et al, 1998). The protein CD47 is consisting of an extracellular immunoglobin-like domain, five segments spanning the membrane and an intracellular tail (Jiang et al, 1999). CD47 is expressed in many cell types including normal and cancerous cells. SIRPα, on the other hand, is only expressed in macrophages, neurons, dendritic cells and neutrophils. During developmental stages, CD47 and SIRPα are both expressed in the brain suggesting that anti-phagocytic signals dominate to allow for proper cell proliferation. Cancer takes advantage of this mechanism to avoid cell death. The introduction of antibodies that prevents CD47-SIRPα interaction ultimately inhibiting the "don't eat me" signal (Jiang et al, 1999). The silencing of the anti-phagocytic signal does not directly result to the engulfment of the cell. The positive phagocytic signals must be reflected in the net signal transmission of the cell. These pro-phagocytic signals are induced by the surface of exposure of phosphatidylserine and calreticulin. |
The interaction between CD47 and SIRPα may have bidirectional signalling consequences (Figure 8):
1. Cdc42 activation promoting the positive modulation of pathways involved in growth, migration and cell structure development (Muruta et al, 2006). 2. Binding of phosphatases SHP1 and SHP-2 activate phagocytotic inhibition. (Okazawa et al, 2005) |