論文 - 詳細
RRC ID | 73435 |
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著者 | Ohsawa I, Murakami T, Uemoto S, Kobayashi E. |
タイトル | In vivo luminescent imaging of cyclosporin A-mediated cancer progression in rats. |
ジャーナル | Transplantation |
Abstract |
BACKGROUND:Immunosuppressed individuals undergoing organ transplantation are at increased risk of recurrences of initial cancers, although how immunosuppressive therapy increases early cancer metastasis remains unclear. METHODS:The metastatic fate of luciferase-expressing rat metastatic colon cancer cells (luc-RCN-H4) injected intravenously into the liver of syngeneic and allogeneic rats was examined in the presence of the immunosuppressant cyclosporin A (CsA) by in vivo luminescent technique. With respect to potential tumor-progressing factors, contribution of chemokine receptors and transforming growth factor (TGF)-beta1 to early metastasis was evaluated using their specific signaling inhibitors. RESULTS:F344 rats injected in the liver with luc-RCN-H4 cells did not always exhibit the formation of tumors and showed a dormant state as long as 60 days after inoculation without CsA. However, CsA released early luc-RCN-H4 cells from dormancy within 2 weeks at nearly 100% in liver and preferentially promoted metastasis to the lymph nodes (approximately 40%). A similar dissemination occurred even in minor histocompatibility complex-disparate hosts. As a tumor-progressing factor, RCN-H4 cells aberrantly expressed chemokine receptors CXCR4 and CCR7. The chemokine receptor (CXC) R4-specific antagonist AMD3100 decreased early metastasis of luc-RCN-H4 cells in rats with ischemic liver conditions (P<0.05), but CsA treatment did not enhance early adhesion. Use of CsA was able to facilitate TGF-beta1 expression and the subsequent TGF-beta-mediated random migration was blocked by the use of the specific signaling inhibitor SB431542 in vitro. CONCLUSIONS:Whereas the chemokine receptor expression by cancer cells is implicated with early organotropic dissemination even under CsA-mediated immune suppression, rather, CsA enhances the late-phase progression after tumor adhesion through TGF-beta1 expression. |
巻・号 | 81(11) |
ページ | 1558-67 |
公開日 | 2006-6-15 |
DOI | 10.1097/01.tp.0000209448.50238.de |
PII | 00007890-200606150-00010 |
PMID | 16770245 |
MeSH | Adenocarcinoma / chemistry Adenocarcinoma / genetics Adenocarcinoma / pathology* Animals Benzamides / pharmacology Blotting, Western Cell Adhesion Cell Line, Tumor Cell Movement / drug effects Colonic Neoplasms / immunology Colonic Neoplasms / pathology* Cyclosporine / adverse effects* Cyclosporine / pharmacology* Dioxoles / pharmacology Disease Progression Gene Expression Regulation, Neoplastic / drug effects Image Processing, Computer-Assisted / methods* Killer Cells, Natural / drug effects Killer Cells, Natural / pathology Liver Neoplasms / genetics Liver Neoplasms / immunology Liver Neoplasms / secondary Luminescence Lymphatic Metastasis / immunology Male Neoplasm Metastasis / pathology Rats Rats, Inbred F344 Receptors, Chemokine / analysis Receptors, Chemokine / genetics Reperfusion Injury / pathology Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta / analysis Transforming Growth Factor beta / genetics Transforming Growth Factor beta1 |
IF | 4.546 |
リソース情報 | |
ヒト・動物細胞 | RCN-9(RCB0511) |