Exosomes increased angiogenesis in papillary thyroid cancer microenvironment

Author:

Wu Feng12,Li Fuxingzi3,Lin Xiao34,Xu Feng3,Cui Rong-Rong3,Zhong Jia-Yu34,Zhu Ting3,Shan Su-Kang3,Liao Xiao-Bo5,Yuan Ling-Qing3,Mo Zhao-Hui1

Affiliation:

1. 1Department of Endocrinology, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

2. 2Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

3. 3Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

4. 4Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

5. 5Department of Cardiovascular Surgery, the Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People’s Republic of China

Abstract

Tumour-derived exosomes under hypoxic conditions contain informative miRNAs involved in the interaction of cancer and para-carcinoma cells, thus contributing to tissue remodelling of the tumour microenvironment (TME). Exosomes isolated from hypoxic papillary thyroid cancer cells, BCPAP cells and KTC-1 cells enhanced the angiogenesis of human umbilical vein endothelial cells (HUVECs) compared with exosomes isolated from normal thyroid follicular cell line (Nthy-ori-3-1), normoxic BCPAP or KTC-1 cells both in vitro and in vivo. miR-21-5p was significantly upregulated in exosomes from papillary thyroid cancer BCPAP cells under hypoxic conditions, while the exosomes isolated from hypoxic BCPAP cells with knockdown of miR-21-5p attenuated the promoting effect of angiogenesis. In addition, our experiment revealed that miR-21-5p directly targeted and suppressed TGFBI and COL4A1, thereby increasing endothelial tube formation. Furthermore, elevated levels of exosomal miR-21-5p are found in the sera of papillary thyroid cancer patients, which promote the angiogenesis of HUVECs. Taken together, our study reveals the cell interaction between hypoxic papillary thyroid cancer cells and endothelial cells, elucidating a new mechanism by which hypoxic papillary thyroid cancer cells increase angiogenesis via exosomal miR-21-5p/TGFBI and miR-21-5p/COL4A1 regulatory pathway.

Publisher

Bioscientifica

Subject

Cancer Research,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism

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