title: A new mechanism for pillar formation during tumor-induced intussusceptive angiogenesis: inverse sprouting.
abstract: One of the hallmarks of intussusceptive angiogenesis is the development of intraluminal connective tissue pillars. The exact mechanism of pillar formation has not yet been elucidated. By using electron and confocal microscopy, we observed intraluminal nascent pillars that contain a collagen bundle covered by endothelial cells (ECs) in the vasculature of experimental tumors. We proposed a new mechanism for the development of these pillars. First, intraluminal endothelial bridges are formed. Second, localized dissolution of the basement membrane occurs and a bridging EC attaches to a collagen bundle in the underlying connective tissue. A pulling force is then exerted by the actin cytoskeleton of the ECs via specific attachment points, which contain vinculin, to the collagen bundle, resulting in suction and subsequent transport of the collagen bundle into and through the vessel lumen. Third, the pillar matures through the immigration of connective tissue cells and the deposition of new collagenous connective tissue. The proposed simple mechanism generates a connection between the processes of endothelial bridging and intussusceptive angiogenesis and identifies the source of the force behind pillar formation. Moreover, it ensures the rapid formation of pillars from pre-existing building blocks and the maintenance of EC polarity. To describe it, we coined the term inverse sprouting.
authors.affiliation: 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. paku@korb1.sote.hu
authors.forename: Sándor
authors.initials: S
authors.lastname: Paku
authors.forename: Katalin
authors.initials: K
authors.lastname: Dezso
authors.forename: Edina
authors.initials: E
authors.lastname: Bugyik
authors.forename: József
authors.initials: J
authors.lastname: Tóvári
authors.forename: József
authors.initials: J
authors.lastname: Tímár
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.forename: Viktoria
authors.initials: V
authors.lastname: Laszlo
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Balázs
authors.initials: B
authors.lastname: Döme
mesh_terms: D000818:Animals; D002196:Capillaries; D045744:Cell Line, Tumor; D003094:Collagen / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology; D012867:Skin / Q000098:blood supply; D014183:Transplantation, Heterologous
chemical_list: D003094:Collagen