Relation of immune semaphorin/plexin signaling to carcinogenesis.

Semaphorins and plexins represent a highly conserved group of proteins that have recently been found to exert widespread regulatory functions outside the nervous system, including angiogenesis and immune regulation. Furthermore, these molecules are definitely implicated in the etiology of carcinogenesis and immune disorders. Their expression patterns and levels are deregulated in cancer cells and in cells of the tumor milieu. During the multistep development of cancer, its characteristic features include sustained tumor cell proliferation, resistance to cell death, limitless replicative capacity, activation of angiogenesis along with invasion and metastatic spread, cancer-related smoldering inflammation, and evasion of antitumor immune responses. The diversity of the semaphorin/plexin complexes and, thus, the multiple stimulated molecular interactions allow varied and diverse cell signaling events. The elicited transduction pathways might be involved in modifying the intricate mechanisms of tumorigenesis. Indeed, these pleiotropic signals may influence not only the intrinsic properties of cancer cells but they could also represent a possible link in mediating the cross-talk between tumor cells and the surrounding multiple stromal cells. In tumorigenesis, however, a dual role of different semaphorins is proposed, as some of them may elicit tumor regression, whereas others definitely promote cancer cell survival and progression. The current antitumoral or prosurvival responsiveness to semaphorins is mainly cell context dependent; nevertheless, their precise relation to cancer networks has not yet been fully elucidated. Here, we survey the many faces of a subset of the large semaphorin family, termed immune semaphorins, in carcinogenesis.