title: Zone-specific remodeling of tumor blood vessels affects tumor growth.
abstract: BACKGROUND
  Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet.
  
  
  METHODS
  By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones.
  
  
  RESULTS
  The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative.
  
  
  CONCLUSIONS
  The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging.
authors.affiliation: Department of Urology, University Hospital Grosshadern, Munich, Germany.
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Nerbil
authors.initials: N
authors.lastname: Kilic
authors.forename: Sema
authors.initials: S
authors.lastname: Sevinc
authors.forename: Friedrich
authors.initials: F
authors.lastname: Zywietz
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Suleyman
authors.initials: S
authors.lastname: Ergun
mesh_terms: D001808:Blood Vessels / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic