A complement for cancer?

A protein belonging to part of the immune system that researchers once hoped to harness to attack cancer cells actually spurs tumor growth, according to a study reported in linkurl:__Nature Immunology.__;http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.1655.html Researchers knocked out a receptor for one of a group of 30 proteins called linkurl:complement proteins,;http://www.the-scientist.com/article/display/23823/ part of the body's normal immune defense repertoire, and observed decreased tumor growth in a mouse model. "This elegant study puts complement in the row of factors that can enhance tumor growth," said Arko Gorter, an immunologist at Leiden University Medical Center in the Netherlands, who was not involved in the study. Complement cascade is made up of about 30 proteins that cleave one another in a series of reactions that radiates from an initial binding site on a pathogen. Best known for its action against bacteria, complement proteins can kill a bacterium without the help of immune cells by burrowing into the bacterial membrane and creating a doughnut-shaped hole. Researchers had thought complement could be used to fight cancers as part of an antibody-based vaccine, as antibody binding is one of the factors that can set off a complement cascade. However, some complement components, such as complement 5a (C5a), act as strong mediators of inflammation. Because in some cases inflammation can promote cancer growth, John Lambris at the University of Pennsylvania and colleagues decided to investigate whether C5a instigated tumor growth through an inflammatory pathway. Lambris' team developed a knock-out mouse for the C5a receptor, which is expressed on a number of tissue types. They observed less tumor growth, as well as an increase in anti-tumor CD8+ T cells. The result suggested that the absence of the C5a receptor on suppressor cells blocks the activation of these cells, allowing the tumor fighting cells to attack the tumor. But according to Gorter, this mechanism may not be the only way that complement excites tumor growth. Tumor microenvironments are complex, said Gorter: "A tumor consists of the real cancer cells, the stroma, and a third component: the inflammatory cells," which can be active or suppressed. While it's clear that complement plays an important role in tumor growth, given the complexity of the tumor microenvironment, it's not completely clear how complement exerts its function, or what triggers it, he said. What remains to be seen, said Gorter, is "how general this mechanism is." Is the C5a effect the researches observed particular to the mouse model used? Will it be true for other cancers? Would it translate to human disease? Despite these questions, which must be addressed with further studies, said Gorter, "It is still an impressive study showing to my knowledge for the first time that complement (C5a) can promote tumor progression."Correction (September 30): When originally posted, the article read that a knockout of one of a group of nine proteins resulted in a decrease in tumor growth. The paragraph should have read that a receptor for one of the 30 proteins was knocked out, resulting in a decrease - rather than an increase - in tumor growth. The problem was corrected. __The Scientist__ regrets the error.

A complement for cancer?

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