Zoledronic acid inhibits thyroid cancer stemness and metastasis by repressing M2-like tumor-associated macrophages induced Wnt/β-catenin pathway

Life Sciences
Juan LvZhi-Yong Deng

Abstract

This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/β-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-li...Continue Reading

Citations

Jul 24, 2020·Cancer Cell International·Zeeshan JavedWilliam C Cho
Feb 24, 2021·Signal Transduction and Targeted Therapy·Xiaonan XiangXiao Xu
May 1, 2021·Cancers·Ewa CendrowiczTomasz P Rygiel
May 12, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Jingshan CaiShengjun Wang

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