Immunohistochemical studies on endothelial cell phenotype in hepatocellular carcinoma

Abstract

and functionally from ordinary endothelia. 2,3 SECs play an To examine the phenotype of the sinusoidal endothelial important role in the receptor-mediated clearance of various cells (SECs) surrounding tumor cells and the process of capilmacromolecules from the blood, including small particulate larization in hepatocellular carcinoma (HCC), 51 primary substances. In chronic hepatitis and cirrhosis, SECs frequently undergo CD4, CD14, and/or CD32 were found on HCC SECs only in transformation into capillary ECs possessing a basement 12 well-differentiated primary HCCs showing a thin trabecumembrane and no fenestrae, i.e., capillarization, 13 and they lar or pseudoglandular tumor cell arrangement. These 12 tulose some of their phenotypic features (including FcR expresmors were smaller than those without CD4-, CD14-, and/or sion) regardless of whether sinusoidal capillarization oc-CD32-positive SECs (P õ .05). Among them, 7, 5, and 11 curs. 8,14 In hepatocellular carcinoma (HCC), the endothelia tumors were negative or only partially positive for laminin, of the sinusoids, i.e., the blood vessels surrounding tumor PAL-E Ag, and FVIIIRAg, respectively. Staining for laminin cells, is generally considered to resemble the capillary endoand PAL-E Ag showed an inverse relationship to the expresthelia, 15,16 but several studies have indicated that the sinusoision of CD4, CD14, and CD32 on HCC SECs and the tumor dal endothelia of early HCC contains Kupffer cell-like macdifferentiation. In conclusion, the phenotypes of the SECs in rophages, 17,18 and shows morphological characteristics early and well-differentiated HCC are thought to be similar intermediate between those of ordinary capillary endothelia to those of the SECs in normal liver. With progressing tumor and the sinusoidal endothelia in normal liver. 19,20 It seems dedifferentiation the HCC SECs lose the phenotypes peculiar that the phenotypes of the SECs in HCC (HCC SECs) graduto liver SECs and acquire the characteristics of capillary ECs, ally changes into that of capillary ECs with tumor progresthough both types of phenotypical change occur indepension. However, the change in the expression of the receptors dently of each other. (HEPATOLOGY 1997;26:407-415.) and adhesion molecules specifically detected on SECs are unclear. This is important for understanding not only the Hepatic sinusoidal endothelial cells (SECs) are unique biological nature of HCC SECs, which are major stromal cells endothelial cells (ECs), which possess fenestrae and no basesupporting HCC cells, but also the pathobiology of sinusoidal ment membrane, and reside together with tissue-fixed macrocapillarization. phages, i.e., Kupffer cells. 1 SECs differ both morphologicallyIn the present study, to analyze the relationship between the phenotypes of SECs and sinusoidal capillarization in

Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice

“…The animals were sacrificed at 1 week and the liver and other organs excised and processed for immunohistochemistry (IHC) and Western blot analysis. Confocal fluorescent microscopy of liver from HA-or ASOR-treated or control animals was performed after IHC using anti-CD14 as a marker for LSECs (29). The results indicated that when ASOR was used as targeting ligand (Figure 2A, top row), DsRed2 was expressed in hepatocytes and exhibited no apparent colocalization with CD14.…”

“…Thin sections (6 μm) were cut and fixed for 10 minutes in -20°C acetone, followed by 3 PBS washes at 4°C. The LSECs were identified by IHC using anti-CD14 primary Ab, specific for the discontinuous liver endothelial cells (29), and a Cy5-labeled secondary Ab. Additional cryosections of the ASOR nanocapsule-treated livers were processed for staining of hepatocyte nuclei using SYTOX green (Invitrogen).…”

A blood–tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds

“…In a similar way, electron microscopy studies revealed the existence of ultrastructural changes in tumor microvasculature, which include the presence of a continuous non-fenestrated endothelium and the deposition of extracellular matrix between endothelium and the neoplastic cells. [31][32][33][34] Immunohistochemical studies [35][36][37][38][39] have shown that this extracellular matrix consists mainly of LN, FN and collagen type IV. In the present work we have observed that as tumor nodules become larger there is a higher expression of ␣-SMA and a more prominent deposition of LN and FN.…”

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

“…Second, the two main characteristics of arterialization and sinusoidal capillarization in HCC developed from OAH gradually increase following lesions progression [58], suggesting a continuous remodeling of tumor vasculature from the pre-existing vessels. CD4, CD14, and CD32, the specific phenotypes of LSECs expressed in early and well-differentiated HCC cases are similar to those of the LSECs in normal liver, but they are not expressed in poorly differentiated HCC [93] suggesting a regression or differentiation of pre-existing vasculature after being integrated into tumor vasculature. Third, the rate of LSEC proliferation is low-from 0.02 to 0.03-in HCC [82] suggesting that other source(s) of endothelial cells including vessel co-option should exist in addition to conventional angiogenesis for the rapid establishment of tumor vasculature.…”