Enhanced CD34 expression of sinusaid‐like vascular endothelial cells in hepatocellular carcinoma

Abstract

The immunohistochemical expression of CD34 (human hematopoietic stem cell and endothelial cell marker) and laminin were studied in chronic liver diseases and hepatocellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous sinusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and laminin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and perinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothelial cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.

Cocktail therapy with a combination of interferon, ribavirin and angiotensin-II type 1 receptor blocker attenuates murine liver fibrosis development

“…In liver fibrosis, it has been shown that VEGF expression increased both in human chronic liver diseases and in experimental fibrogenesis (59)(60)(61). It has also been reported that VEGF expression correlates with chronic liver disease-associated angiogenesis and sinusoidal capillarization (59,62,63). We also observed that VEGF gene expression significantly increased during fibrosis development associated with neovascularization in the liver, and that the suppression of VEGF-receptor interaction significantly attenuated the progression of liver fibrosis and angiogenesis (25).…”

A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment

“…The FoxM1 transcription factor was identified as a novel inhibitory target of the mouse ARF tumor suppressor, and structure-function studies demonstrated that amino acid residues 26-46 of the mouse ARF protein were sufficient to inhibit FoxM1 (8). Furthermore, treatment of osteosarcoma U2OS cells with a cell-penetrating ARF [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] peptide containing 9 N-terminal d-arginine (D-Arg) residues (WT ARF [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] ) (32,33) significantly reduced FoxM1 function in this cancer cell line (8). Moreover, we previously developed Tg mice in which the Rosa26 promoter was used to drive ubiquitous expression of the human FoxM1b cDNA, and increased FoxM1b levels stimulated proliferation of pulmonary cells in response to lung injury (34) and stimulated development and progression of prostate cancers in both TRAMP/Rosa26-FoxM1b and LADY/Rosa26-FoxM1b double-Tg mice <...>…”

Novel endothelial cell markers in hepatocellular carcinoma

“…CD34 is known to be strongly expressed in the sinusoidal endothelial cells in HCC by immunohistochemistry (IHC) compared with nontumor liver tissues, whereas antibodies against CD31 and vWF only stain a small number of sinusoidal endothelial cells in HCC and at lower intensity. 18,19 Recent evidence suggests that the phenotypic diversity of tumors is associated with corresponding diversity in their gene expression programs. cDNA microarray technology has been used to study gene expression patterns in different tumor types and has provided new insight into the development and classification of these cancers.…”