Extracellular Vesicles as Signal Carriers in Malignant Thyroid Tumors?

Abstract

Extracellular vesicles (EVs) are small, membranous structures involved in intercellular communication. Here, we analyzed the effects of thyroid cancer-derived EVs on the properties of normal thyroid cells and cells contributing to the tumor microenvironment. EVs isolated from thyroid cancer cell lines (CGTH, FTC-133, 8505c, TPC-1 and BcPAP) were used for treatment of normal thyroid cells (NTHY), as well as monocytes and endothelial cells (HUVEC). EVs’ size/number were analyzed by flow cytometry and confocal microscopy. Gene expression, protein level and localization were investigated by qRT-PCR, WB and ICC/IF, respectively. Proliferation, migration and tube formation were analyzed. When compared with NTHY, CGTH and BcPAP secreted significantly more EVs. Treatment of NTHY with cancer-derived EVs changed the expression of tetraspanin genes, but did not affect proliferation and migration. Cancer-derived EVs suppressed tube formation by endothelial cells and did not affect the phagocytic index of monocytes. The number of 6μm size fraction of cancer-derived EVs correlated negatively with the CD63 and CD81 expression in NTHY cells, as well as positively with angiogenesis in vitro. Thyroid cancer-derived EVs can affect the expression of tetraspanins in normal thyroid cells. It is possible that 6 μm EVs contribute to the regulation of NTHY gene expression and angiogenesis.

Agrin is a novel oncogenic protein in thyroid cancer

“…A cell line derived from anaplastic carcinoma (8505C) was generously provided by Dr Cuong Hoang-Vu (Martin Luther University; Halle, Germany). All cell lines were authenticated by immunofluorescence with tetraspanins including CD9, CD63, CD81, CD82 and CD151 ( 29 ). Analyzed cell lines were cultured according to the supplier's protocols as follows: i) NTHY and CGTH cell lines cultured in complete RPMI-1640 medium; ii) FTC-133 and 8505C cell lines in DMEM/F12 and iii) BcPAP cell line in complete DMEM/GlutaMAX™ (all Thermo Fisher Scientific, Inc.).…”

Role of Extracellular Vesicles in Thyroid Physiology and Diseases: Implications for Diagnosis and Treatment

“…Besides these studies highlighting the role of EVs in malignancy, it is important to mention that contrasting results were also recently reported. The effect of EVs isolated from different thyroid cancer cell lines (CGTH, FTC-133, 8505c, TPC-1 and BCPAP) was assessed on Nthy-ori 3.1 without demonstrating any significant effect on proliferation, migration and invasion [ 29 ].…”

“…Proteins implicated in integrin signaling, tumor-promoting pathways, neutrophil degranulation and angiogenesis were also more abundant in ATC-EVs [ 26 ]. Functionally, cancer-derived EVs negatively affected HUVEC tube formation but did not change monocyte phagocytosis [ 29 ]. The crosstalk between tumoral or normal thyroid cells (TPC-1, 8505c, Nthy-oi 3-1) and fibroblasts was studied in co-culture experiments.…”