title: Dormant tumors awaken by a short-term angiogenic burst: the spike hypothesis.
abstract: Tumor dormancy, a complex and still poorly understood phenomenon observed both in experimental models and in patients, has been associated with insufficient angiogenic capacity. A defined event, termed "angiogenic switch" and characterized by an imbalance between pro- and anti-angiogenic factors, often marks interruption of the dormant state, thus triggering invasive tumor growth. In our current view, sustained angiogenesis is considered essential in promoting this transition. Recently, we demonstrated that co-administration of proliferation-arrested Kaposi's sarcoma cells or recombinant angiogenic factors interrupts dormancy of poorly angiogenic leukemia cells by providing a brief angiogenic burst. These findings indicate that even a transient angiogenic switch can prime progressive tumor growth and suggest that tumor angiogenesis is a process requiring a higher amount of angiogenic factors for its induction than maintenance. Here we discuss the implications of these observations on our view of tumor angiogenesis and on the therapeutic potential of angiogenesis inhibitors.
authors.affiliation: Istituto Oncologico Veneto, Padova, Italy. stefano.indraccolo@unipd.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Elena
authors.initials: E
authors.lastname: Favaro
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D000068258:Bevacizumab; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab