Skip Navigation LinksHome > November 2011 - Volume 70 - Issue 11 > Lack of Angiogenesis in Experimental Brain Metastases
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e318233afd7
Original Articles

Lack of Angiogenesis in Experimental Brain Metastases

Bugyik, Edina MS; Dezső, Katalin MD; Reiniger, Lilla MD, PhD; László, Viktória PhD; Tóvári, József PhD; Tímár, József MD, PhD, DSc; Nagy, Péter MD, PhD; Klepetko, Walter MD; Döme, Balázs MD, PhD; Paku, Sándor PhD

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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.

© 2011 American Association of Neuropathologists, Inc

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