Infection & neoplastic growth 101: the required reading for microbial pathogens aspiring to cause cancer

Abstract

The role of infectious agents in the development of cancer is well-established. For example, numerous RNA and DNA viruses express dedicated oncoproteins that are able to transform cells in vitro and induce rapid tumor formation in experimental animals. Curiously, these acutely-transforming viruses are seldom associated with naturally occurring neoplasms of humans or animals. Conversely, the microbial pathogens that are linked to cancers in natural hosts rarely encode acutely transforming proteins. Moreover, they tend to down-regulate most of their genes except for genes affecting cell survival, often via the NF-kappaB pathway. This allows the pre-neoplastic cell to avoid triggering cytotoxic immunity and the ensuing acute inflammation. These host responses not only kill tumor cells directly, but also strongly suppress the development of new blood vessels (neovascularization), which is absolutely essential for neoplastic growth. Chronic inflammation, on the other hand, promotes neoplastic cell growth and may even be conducive to neovascularization. Thus, cancer-associated microbial pathogens must follow the "less is more" principle. According to this principle, only minor perturbations in cell proliferation and death are tolerated by the host, but in the long run, they are all that is necessary for tumorigenesis.