title: Lack of angiogenesis in experimental brain metastases.
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.
authors: 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University.
authors: Edina
authors: E
authors: Bugyik
authors: Katalin
authors: K
authors: Dezso
authors: Lilla
authors: L
authors: Reiniger
authors: Viktória
authors: V
authors: László
authors: József
authors: J
authors: Tóvári
authors: József
authors: J
authors: Tímár
authors: Péter
authors: P
authors: Nagy
authors: Walter
authors: W
authors: Klepetko
authors: Balázs
authors: B
authors: Döme
authors: Sándor
authors: S
authors: Paku
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002277:Carcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D055032:Electron Microscope Tomography; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000378:metabolism; D034882:Lamins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C543505:INTS3 protein, human; D034882:Lamins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011804:Quinolines; C495966:TOTO-3 compound; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D007633:Keratins; D020797:Receptor, Platelet-Derived Growth Factor beta; D001973:Bromodeoxyuridine