Involvement of liver-associated immunity in hepatic metastasis formation
| Autor: | Kiyotaka Okuno, Hironori Shigeoka, Yung Sun Lee, Norihiko Hirai, Masayuki Yasutomi, Isao Kawai |
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| Rok vydání: | 1998 |
| Předmět: |
Cytotoxicity
Immunologic Pathology medicine.medical_specialty medicine.medical_treatment Lymphocyte Clone (cell biology) Adenocarcinoma Metastasis Immune system MHC class I medicine Tumor Cells Cultured Cytotoxic T cell Animals Lymphocytes biology Histocompatibility Antigens Class I Liver Neoplasms Immunity medicine.disease Interleukin-12 Rats Inbred F344 Rats Cytokine medicine.anatomical_structure Liver Colonic Neoplasms biology.protein Interleukin 12 Cancer research Surgery Neoplasm Transplantation |
| Zdroj: | The Journal of surgical research. 75(2) |
| ISSN: | 0022-4804 |
| Popis: | Aims.Hepatic metastasis formation and prevention were studied from the viewpoint of liver-associated immunity. Methods.RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, in which the cancer is highly metastatic to the liver, were used. Fischer rats that were inoculated with parent RCN-9 colonic cancer cells (5 × 106) via the portal vein showed liver metastasis in less than 60% of the animals. In contrast, all rats (100%) that received RCN-H4 produced multiple liver metastases. To investigate the difference of hepatic metastasis formation, we assessed the susceptibility of both cell lines against hepatic sinusoidal lymphocytes (HSL) by51Cr-release assay, and the expression of MHC class I and class II of both cell lines by flow cytometry. In addition, we examined whether activation of HSL by interleukin-12 (IL-12) can prevent liver metastasis of highly metastatic clone RCN-H4. Results.The RCN-H4 clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL. This decrease in susceptibility was attributable to an increase in cell surface expression of MHC class I antigen. Administration of IL-12, a potent NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4 clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein. Conclusions.Liver metastasis formation is positively correlated with the strength of the hepatic immune system which mainly consists of ontogenetically primitive T cells. As these effectors exert their cytotoxicity in a MHC-nonrestricted fashion, tumor cells that highly express MHC class I antigen can readily avoid hepatic surveillance and apt to cause liver metastasis. Augmentation of the hepatic immune system, for instance, with IL-12 administration, can prevent liver metastasis even in tumor cells with a high potential for liver metastasis. |
| Databáze: | OpenAIRE |
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