Potential implication of IL-24 in lymphangiogenesis of human breast cancer

Frewer, Natasha, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Sun, Ping-Hui, Owen, Sioned, Ji, Ke, Frewer, Kathryn A., Hargest, Rachel ORCID: https://orcid.org/0000-0001-9830-3832 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2013. Potential implication of IL-24 in lymphangiogenesis of human breast cancer. International Journal of Molecular Medicine 31 (5) , pp. 1097-1104. 10.3892/ijmm.2013.1319

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	interleukin-24, MDA-7, lymphangiogenesis, breast cancer
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/1107-3756/ (accessed 21/07/2014).
Publisher:	Spandidos Publications
ISSN:	1107-3756
Funders:	Royal College of Surgeons of England, Breast Cancer Hope Foundation, Albert Hung Foundation, Cancer Research Wales
Date of First Compliant Deposit:	30 March 2016
Last Modified:	11 Oct 2023 17:13
URI:	https://orca.cardiff.ac.uk/id/eprint/61483

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