Buried alive: a novel approach to cancer treatment.
The heightened interest in the development of novel anti-cancer drugs that trigger apoptotic death in cancer cells stems from the fact that immediately upon execution of the death signal, the corpse is efficiently removed via specific recruitment of phagocytic cells. This prevents spilling of cellular contents and the associated inflammatory response, a likely scenario during necrotic death. Recent evidence has established that phagocytic removal of apoptotic cells is a function of ligand-receptor interaction, whereby the ligand(s) for the scavenger receptor(s) of phagocytic cells is/are specifically expressed on apoptosing cells. Therefore, by implication, enhancing this ligand-receptor interaction could be an alternate means for removing unwanted cells. Here we present a provocative hypothesis that circumvents the need for chemotherapy-induced apoptosis in cancer cells. According to our model, cancer cells need not die in order to be removed by scavenger cells, but could still be effectively phagocytosed provided the cell surface expression of specific molecules that strongly engage phagocytic cells is sufficiently enhanced. In other words, inducing the expression of "eat me" signals on cancer cells could be a novel approach to "bury alive" these unwanted cells without the untoward effects of chemotherapy-induced apoptosis.
Fadeel
Bengt
B
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Orrenius
Sten
S
Pervaiz
Shazib
S
D017209:Apoptosis; D006801:Humans; D008565:Membrane Proteins; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B