Morphological study of vascular dissemination in a metastatic hepatocellular carcinoma model in the monkey

Abstract

In this report we describe a metastatic monkey hepatocellu-cinoma (HCC) has been associated with several types of liver diseases such as hepatitis and cirrhosis. 10,11 In HCC, the lar carcinoma (HCC) model in which intravascular metastatic development is clearly evident. The tumor-bearing livers con-phase of accelerated tumor growth and metastasis appears to coincide with the emergence of the tumor vasculature, which tained intravenous tumor thrombi at different stages of progression within the small branches of the portal vein. These is derived mainly from the hepatic artery.12,13 HCC frequently disseminates intrahepatically through the portal vascular ranged from mural tumor thrombi lined with CD31-positive endothelial cells to tumor thrombi that had completely oc-channels.14 Tumor microemboli are often found in the circulation of patients with HCC and renal carcinoma. This has cluded the vascular lumen. Intravenous tumor expansion was frequently accompanied by the appearance of CD31-positive been linked to the propensity of these tumors to invade local microvessels within the tumor thrombi and fibrous perivascu-venous structures. [14][15][16][17] In rodent models, the cellular and lar thickening, giving rise to isolated tumor nodules within biochemical aspects of hepatocarcinoma genesis have been the portal areas. Intravascular expansion of disseminating studied extensively. 18 In the present monkey carcinogenesis HCC was also evident within small branches of the pulmonary model, HCC was induced by a food-derived heterocyclicaarteries in the lungs. These findings indicate that metastases mine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), which of HCC can become established while still at an intravascular was previously reported to be a multiorgan carcinogen in stage, suggesting that the direct interaction between tumor rodents.19 This nonhuman primate model provided a rare cells and parenchymal cells predicted from experimental ro-opportunity to study the morphology of intrahepatic vascular dent metastasis models is not a prerequisite for the metastatic dissemination and seeding of tumor cells in the pulmonary development of these tumors. (HEPATOLOGY 1997;26:1209-vasculature by chemically induced HCC. The results pre-1215. ) sented here suggest that the intravascular phase of metastatic development in HCC is more prolonged than has been predicated from rodent metastasis models. Tumor metastasis is a complex multi-step process.1,2 Studies of the metastatic process using rodent models, in which MATERIALS AND METHODShighly invasive tumor cells are injected into the systemic Monkey Tissues. The tissues used in this study were obtained from circulation, have led to the proposal that tumor cells must 34 cynomolgus monkeys (Macaca fascicularis), who developed liver be able to exit the circulation and grow within the organ tumors as a result of chronic exposure to IQ. 20 These monkeys were parenchyma to form metastases.2 Angiogenesis has also been born and raised in a closed colony and stayed with their mothers s...

Ribonucleotide reductase M2B inhibits cell migration and spreading by early growth response protein 1-mediated phosphatase and tensin homolog/Akt1 pathway in hepatocellular carcinoma

“…The portal vein is the main route for intrahepatic metastases of HCC cells in animal model systems and in human patients. 3,4 Therefore, the identification of metastatic factors and elucidation of the underlying molecular mechanism that are involved in the progression of metastasis become critical issues.…”