Kupffer cells and liver metastasis

Abstract

Kupffer cells, tissue-fixed macrophages located in the sinusoids of the liver, represent the highest concentration of mononuclear phagocytes in the body. Their ability to act as scavengers of particulate material in the blood has given rise to speculation that they play a role in controlling hepatic metastases derived from blood-borne tumor cells. Circumstantial evidence for such a role has been obtained from animal studies where Kupffer cell function has been compromised or inhibited, and from anecdotal clinical observations. Current evidence suggests that Kupffer cells are capable of nonspecifically eliminating some circulating tumor cells from the circulation via phagocytosis. This surveillance mechanism would appear to be limited in capacity, and subject to a number of external factors. Recent studies have demonstrated that Kupffer cells can be activated to a tumoricidal state via the administration of biological response modifiers such as gamma interferon or muramyl peptides. The localization of liposomes within Kupffer cells after systemic administration has provided a considerable stimulus for the efficient targeting of macrophage-activating compounds to these cells. Such therapeutic intervention, while capable of inducing Kupffer cell tumoricidal activity in situ and inhibiting tumor growth, is limited with respect to the location of the tumor cells (sinusoidal versus parenchymal) and to the size of the metastatic nodule. Therapeutic intervention using liposomes containing macrophage-activating agents may only be of benefit in patients with minimal tumor load who are at risk for hepatic metastases, rather than those patients who already have clinically detectable liver tumors.

Desialylation of metastatic human colorectal carcinoma cells facilitates binding to Kupffer cells

“…The liver is the largest reticuloendothelial organ in the body, with Kupffer cells making up over 80% of the body's fixed macrophage population [20]. Previous studies have shown that Kupffer cells possess considerable tumoricidal activity against a variety of tumor cell targets [21][22][23].…”

An electron microscopy study of Kupffer cells in livers of mice having Friend erythroleukemia hepatic metastases

“…However, activated Kupffer cells still leave a residual burden of tumor cells that can continue to metastasize. As the hepatic tumor load increases the Kupffer cell population within tumor vessels decreases [6]. Kupffer cell depletion is thought to be a factor in the development of hepatocellular carcinoma [41] and in the formation of carcinogeninduced hepatic nodules that eventually become carcinomas [17].…”

“…Previous studies demonstrated that Kupffer cells and other macrophages can be activated to a tumoricidal state by administering biological response modifiers (BRMs) such as lipopolysaccharide [11][12][13]20], gamma interferon [11,12,21,22] and muramyl peptides [6,7,20,23,24] resulting in reduced tumor load and increased survival time. The close proximity of Kupffer cells to liver metastases makes them an attractive target for immunomodulatory therapy to stimulate macrophage defense [7,10,12].…”

“…Kupffer cells in hepatic sinusoids are not only tumoricidal [6,7,[13][14][15], but can directly phagocytose tumor cells [1,16]. Within 24 h after exposure to tumor cells, the number of Kupffer cells in the hepatic sinusoids dramatically increases [17,18] presumably by influx of precursors from the bone marrow [19].…”

“…Within the hepatic sinusoids reside the largest single population of active macrophages, the Kupffer cells, which are important effector cells in host defense against metastatic tumors [6][7][8][9][10][11][12]. Kupffer cells in hepatic sinusoids are not only tumoricidal [6,7,[13][14][15], but can directly phagocytose tumor cells [1,16].…”