Lack of angiogenesis in experimental brain metastases

Edina Bugyik, Katalin Dezso, Lilla Reiniger, Viktória László, József Tóvári, József Tímár, Péter Nagy, Walter Klepetko, Balázs Döme, Sándor Paku

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Angiogenesis is believed to be essential for the growth of metastatic tumors in the brain. We analyzed the vascularization of tumors formed by 4 epithelial cell lines (C38, ZR75, HT25, and H1650) and a fibrosarcoma (HT1080) cell line injected into the brains of mice. No peritumoral angiogenesis was observed. Tumors apparently acquired their vasculature by incorporation of native vessels. Vessel density was lower, but vessel diameter and vascular cell proliferation were higher within all tumors versus those in the peritumoral tissue. There was an inverse correlation between the number of incorporated vessels and vascular cell proliferation. Epithelial tumors with pushing growth patterns had lower vessel density and elevated vascular cell proliferation compared with invasive tumors. The incorporated vessels retained their normal structure, with the exception of astrocyte foot processes that were replaced by tumor cells. Attachment to the vascular basement membrane led to the differentiation of the ZR75 breast cancer cells. In the HT1080 metastases, there was intussusceptive angiogenesis, that is, the fibrosarcoma cells that were attached to the vessel caused lumen splitting and filled the developing pillars. Branching angiogenesis was not observed either in the tumors or in control cerebral wounds. These data suggest that sprouting angiogenesis is not needed for the incipient growth of cerebral metastases and that tumor growth in this model is a result of incorporation of host vessels.

Original languageEnglish
Pages (from-to)979-991
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume70
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

Keywords

  • Angiogenesis
  • Astrocyte
  • Brain
  • Carcinoma
  • Endothelial cell
  • Fibrosarcoma
  • Metastasis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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