Blood vessels expressing CD90 in human and rat brain tumors.

Blood vessels in brain tumors, particularly glioblastomas, have been shown to express CD90. CD90(+) cells in and around blood vessels in cancers including brain tumors have been identified as endothelial cells, cancer stem cells, fibroblasts or pericytes. In this study, we aimed to determine the nature or type(s) of cells that express CD90 in human brain tumors as well as an experimental rat glioma model by double immunofluorescence staining. The majority of CD90(+) cells in human glioblastoma tissue expressed CD31, CD34 and von Willebrand factor, suggesting that they were endothelial cells. Vasculatures in a metastatic brain tumor and meningioma also expressed CD90. CD90(+) cells often formed glomeruloid structures, typical of angiogenesis in malignant tumors, not only in glioblastoma but also in metastatic tumors. Some cells in the middle and outer layers of the vasculatures expressed CD90. Similar results were obtained in the rat glioma model. There were cells expressing both α-smooth muscle actin and CD90 in the middle layer of blood vessels, indicating that smooth muscle cells and/or pericytes may express CD90. CD90(+) vasculatures were surrounded by tumor-associated macrophages (TAMs). Thus, in addition to endothelial cells, some other types of cells, such as smooth muscle cells, pericytes and fibroblasts constituting the vasculature walls in brain tumors expressed CD90. Because CD90 has been shown to interact with integrins expressed by circulating monocytes, CD90 might be involved in angiogenesis through recruitment and functional regulation of TAMs in tumors. CD90(+) vasculatures may also interact with tumor cells through interactions with integrins. Because CD90 was not expressed by vasculatures in normal brain tissue, it might be a possible therapeutic target to suppress angiogenesis and tumor growth.

Distribution of the heterogeneity of des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Our aim was to evaluate the heterogeneity of des-gamma-carboxyprothrombin (DCP) in the plasma of patients with hepatocellular carcinoma (HCC), benign liver diseases, and normal controls and compare the DCP values by enzyme-linked immunosorbent assay (ELISA) for two types monoclonal antibodies (MU-3 and 19B7). METHODS: We purified DCP from the plasma of 17 patients with HCC, three patients with metastatic liver tumors (MTLT), 12 with acute hepatitis (AH), five with chronic hepatitis (CH), nine with liver cirrhosis (LC), and 10 normal controls (NC). The DCP was analyzed by using immunoaffinity chromatography, reversed-phase high-performance liquid chromatography and measured by using an ELISA. RESULTS: In HCC, the synthesis of the 1-, 3-, and 4-Gla (gamma-carboxyglutamic acid) DCP variants markedly increased, and those levels accounted for more than 50% of the DCP. The synthesis of the 3-, and 4-Gla DCP gradually increased in order of AH, CH, and LC patients. The MU-3 antibody reacted with the 1-, 3- and 4-Gla DCP variants, whereas the 19B7 antibody reacted with the 6-, 7- and 8-Gla variants. The DCP was measured by ELISA, markedly increased in order of NC, AH, CH, LC, and HCC cases. The correlation of the ratios (1 + 3 + 4)-Gla/(6 + 7 + 8)-Gla DCP and MU-3/19B7 was positive and statistically significant (r = 0.786, n = 56). CONCLUSIONS: According to the severity of liver damages, the synthesis of the 1-, 3- and 4-Gla DCP variants that lost the Ca binding from the outside of the Gla-domain of the prothrombin molecule increases and the MU-3/19B7 ratio is believed to reflect this.