title: The angiostatic protein 16K human prolactin significantly prevents tumor-induced lymphangiogenesis by affecting lymphatic endothelial cells.
abstract: The 16-kDa angiostatic N-terminal fragment of human prolactin (16K hPRL) has been reported to be a new potent anticancer compound. This protein has already proven its efficiency in several mouse tumor models in which it prevented tumor-induced angiogenesis and delayed tumor growth. In addition to angiogenesis, tumors also stimulate the formation of lymphatic vessels, which contribute to tumor cell dissemination and metastasis. However, the role of 16K hPRL in tumor-induced lymphangiogenesis has never been investigated. We establish in vitro that 16K hPRL induces apoptosis and inhibits proliferation, migration, and tube formation of human dermal lymphatic microvascular endothelial cells. In addition, in a B16F10 melanoma mouse model, we found a decreased number of lymphatic vessels in the primary tumor and in the sentinel lymph nodes after 16K hPRL treatment. This decrease is accompanied by a significant diminished expression of lymphangiogenic markers in primary tumors and sentinel lymph nodes as determined by quantitative RT-PCR. These results suggest, for the first time, that 16K hPRL is a lymphangiostatic as well as an angiostatic agent with antitumor properties.
authors.affiliation: GIGA Research, Molecular Biology and Genetic Engineering Unit, University of Liège, 4000 Liège, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Kinet
authors.forename: Karolien
authors.initials: K
authors.lastname: Castermans
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Herkenne
authors.forename: Catherine
authors.initials: C
authors.lastname: Maillard
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Michelle
authors.initials: M
authors.lastname: Lion
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
mesh_terms: D043165:Angiostatic Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects* / Q000473:pathology; D042583:Lymphangiogenesis / Q000187:drug effects*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011388:Prolactin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D043165:Angiostatic Proteins; D010446:Peptide Fragments; C503760:prolactin 16-kDa fragment, human; D011388:Prolactin