Potential implication of IL-24 in lymphangiogenesis of human breast cancer
Lymphangiogenesis is involved in the dissemination of malignant cells from solid tumours to regional lymph nodes and possibly to various distant sites. Lymphangiogenesis is regulated by vascular endothelial growth factor (VEGF)-C and VEGF-D. Interleukin (IL)-24 is known as a cytokine with potent antitumour and tumour-suppressive activity which functions through its receptor (IL-22R). Expression of IL-24 has been shown to be reduced in breast cancer, and the reduced expression is associated with lymphatic metastases and a poor prognosis. However, the involvement of IL-24 in lymphangiogenesis during lymphatic metastasis remains unclear. The aim of the present study was to determine whether there is an association between IL-24, IL-22R and lymphangiogenic factors and markers in breast cancer. Analysis of IL-24, IL-22R and lymphangiogenic factors in malignant breast tissue samples (n=127) revealed a correlation between increased expression of lymphangiogenic markers (podoplanin, Prox-1 and LYVE-1) and reduced levels of IL-24 and IL-22R. Samples stained with a high degree of positivity for lymphangiogenic factors and markers whereas staining for IL-24 was weak. In vitro assays showed that the average perimeter length of microtubules formed by endothelial cells treated with IL-24 was significantly reduced compared to the control. The growth of endothelial cells was significantly reduced when exposed to a high concentration of IL-24 (250 ng/ml). Treatment of HECV cells with IL-24 resulted in significantly reduced expression of VEGF-C (P<0.05) and VEGF-D (P<0.001). In conclusion, reduced expression of IL-24 and IL-22R in breast cancer is correlated with increased expression of specific lymphangiogenic markers. IL-24 suppressed in vitro growth and microtubule formation of endothelial cells. IL-24 may downregulate the expression of lymphangiogenic markers and factors although further research is required. This suggests that IL-24 plays a profound role in suppressing tumour lymphangiogenesis, thereby, reducing the likelihood of cancer metastasis via the lymphatic route.
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Document Type: Research Article
Affiliations: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
Publication date: January 1, 2013
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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