title: New insights into antimetastatic and antiangiogenic effects of cannabinoids.
abstract: Cannabinoids exert antitumorigenic effects via multiple mechanisms. Of these, antimetastatic and antiangiogenic actions have attracted considerable interest in the past years. Regarding the underlying antimetastatic mechanism, several studies revealed cannabinoids to alter the gene expression of cancer cells toward a less-aggressive phenotype and to modulate their secretomic profile. Cannabinoids likewise modulate the release of factors from tumor cells that subsequently suppress the chemoattraction of vessel cells thereby conferring antiangiogenesis. Among the diverse mediators of cannabinoids' antitumorigenic action, the tissue inhibitor of matrix metalloproteinases-1, which is released from cancer cells upon cannabinoid treatment, has been implicated as a pivotal factor conferring both anti-invasive properties of cancer cells as well as antiangiogenic capacities of endothelial cells. In addition, cannabinoids have been shown to inhibit angiogenic capacities of endothelial cells directly via suppressing their proliferation, tube formation, and migration. This chapter reviews the cell- and substance-specific antitumorigenic mechanisms of cannabinoids with particular consideration of their antimetastatic/anti-invasive and antiangiogenic actions. In addition, beneficial interactions of cannabinoids with currently used chemotherapeutics as well as the influence of cannabinoids on tumor-immune surveillance are addressed. Collectively, the currently available data suggest cannabinoids as a potential tool in modern cancer pharmacotherapy.
authors.affiliation: Institute of Toxicology and Pharmacology, University of Rostock, Rostock, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Ramer
authors.affiliation: Institute of Toxicology and Pharmacology, University of Rostock, Rostock, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hinz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002186:Cannabinoids / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002186:Cannabinoids
keywords: Angiogenesis; Cancer; Cannabinoids; Metastasis; Tumor cell invasion