title: Changes in blood vessel maturation in the fibrous cap of the tumor rim.
abstract: It is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Naito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takara
authors.forename: Taku
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawahara
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000068258:Bevacizumab; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
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