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Inhibition ofCyclooxygenase-2Suppresses Lymph NodeMetastasis viaReduction ofLymphangiogenesis Caname IwataMitsunobu R. KanoAkiyoshi Komuro2007 год

Inhibition of Cyclooxygenase-2 Suppresses Lymph Node Metastasis via Reduction of Lymphangiogenesis
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Аннотация: Abstract Cyclooxygenase-2 (COX-2) inhibitor has been reported to suppress tumor progression. However, it is unclear whether this inhibitor can also prevent lymphatic metastasis. To determine the effects of COX-2 inhibitor on lymphatic metastasis, etodolac, a COX-2 inhibitor, was given p.o. to mice bearing orthotopic xenografts or with carcinomatous peritonitis induced with a highly metastatic human diffuse-type gastric carcinoma cell line, OCUM-2MLN. Tumor lymphangiogenesis was significantly decreased in etodolac-treated mice compared with control mice. Consistent with this decrease in lymphangiogenesis, the total weight of metastatic lymph nodes was less in etodolac-treated mice than in control mice. Immunohistochemical analysis revealed that the major source of vascular endothelial growth factor-C (VEGF-C) and VEGF-D was F4/80-positive macrophages in our models. The mRNA levels of VEGF-C in mouse macrophage-like RAW264.7 cells, as well as those in tumor tissues, were suppressed by etodolac. The growth of human dermal lymphatic microvascular endothelial cells was also suppressed by etodolac. Supporting these findings, etodolac also inhibited lymphangiogenesis in a model of chronic aseptic peritonitis, suggesting that COX-2 can enhance lymphangiogenesis in the absence of cancer cells. Our findings suggest that COX-2 inhibitor may be useful for prophylaxis of lymph node metastasis by reducing macrophage-mediated tumor lymphangiogenesis. [Cancer Res 2007;67(21):10181–9]
Год издания: 2007
Авторы: Caname Iwata, Mitsunobu R. Kano, Akiyoshi Komuro, Masako Oka, Kunihiko Kiyono, Erik Johansson, Yasuyuki Morishita, Masakazu Yashiro, Kosei Hirakawa, Michio Kaminishi, Kohei Miyazono
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Lymphatic System and Diseases, Sympathectomy and Hyperhidrosis Treatments, Angiogenesis and VEGF in Cancer
Другие ссылки: Cancer Research (HTML)
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