Experimental approaches for studying semaphorin signals in tumor growth and metastasis in mouse models

Tumor growth and metastatic dissemination are complex multistep processes. They clearly depend on the intrinsic behavior of cancer cells, but are remarkably influenced by a variety of stromal cells present in the tumor microenvironment, which include those implicated in tumor angiogenesis, as well as bone marrow-derived cells recruited from the circulation. Moreover, multiple molecular signals exchanged between cancer cells and non-neoplastic stromal cells control tumor growth and metastasis; notably, members of the semaphorin family are emerging players in this scenario. In vivo tumor models represent the best setting for studying metastatic tumor progression, as they allow recapitulating the contribution of multiple cell types and signaling molecules in a complex tissue context, subject to pathophysiological local and systemic responses, such as metabolic changes, hypoxia, necrosis, fibrosis, inflammation, and cytokine release. Here, we describe some experimental approaches based on murine models to study the role of semaphorin signaling in tumor growth and metastatic progression in vivo.