The role of viruses in cell fusion and its importance to evolution, invasion and metastasis of cancer clones

Abstract

The hypothesis described here is a logical extension of two areas of observation: First, it has been discovered that viruses (and perhaps other intracellular parasites) catalyze cell fusion as a means of cell-to-cell transmission. Effective cell-to-cell transmission appears to require: (i) induced expression of adhesion molecules on the cell surface; (ii) suppression of p53-dependent apoptosis; (iii) arrest of the cell cycle that would otherwise lead to cell death by "mitotic catastrophe". Suppression of apoptosis and cell death through "mitotic catastrophe" are important for formation of stable syncytia. Expression of Bcl-2 or a viral analogue of Bcl-2 (vBcl-2) is particularly useful to viruses because Bcl-2 both suppresses (p53-dependent) apoptosis and arrests the cell cycle through p27. Bcl-2 may also block any p53-independent cell death (e.g., mitotic catastrophe) that is initiated at the mitochondria. Second, it has been found that cell fusion plays a role in cancer clone evolution, invasion of normal cells in tissue adjacent to tumors and metastasis to remote normal tissues. Thus, it can be hypothesized that infection of cancer cells with viruses that spread by cell-to-cell transmission may coincidentally contribute to development of aggressive aneuploid clones and facilitate both invasion and metastasis of tumors. Regardless of the role of viruses, suppression of Bcl-2 may be an approach to preventing successful formation of syncytia and limiting the invasion and metastasis of tumors, thus, making surgical removal and radiation treatment more feasible.