The effect of integrin-linked kinase regulation on chemokine secretions in thyroid cancer
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Date
2016-09-15
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Abstract
Background: The role of immune cell infiltrate in cancer progression has recently become better understood, leading to the development of successful novel treatments. During tumorigenesis, in order to attract pro-malignant immune cells such as including tumor-associated macrophages and regulatory T cells, tumors increase secretion of an array of chemokines, Including RANTES, IP-10, and MIP1-alpha. Our laboratory has previously shown a critical role of the protein integrin-linked kinase (ILK) in the tumor microenvironment of thyroid cancers. We thus planned to assess the role of ILK in chemokine secretion.
Methods: A panel of 5 human thyroid cancer cell lines (papillary cancer lines KTC1, TPC1, BCPAP; follicular cancer line FTC133; anaplastic cancer line hTh112) were transfected with either ILK or control siRNA, in triplicate. Cytokine 65-Plex Discovery Assays (Eve Technologies) were used to assess chemokine secretion.
Results: Successful knockdown of ILK protein expression in all five lines was confirmed via western blot. ILK inhibition led to significantly decreased secretion of RANTES in the cell lines KTC1 (1261 vs 6.8, P<0.01), TPC1 (462.87 vs 5.58, P <0.01), and (??). Similar effects were seen with IP-10 in KTC1 (3773.06 vs 12.86, P<0.01) and TPC1 (2459.66 vs 2.71, P<0.01), as well as MIP1-alpha (KTC1, 223.69 vs 20.7, P<0.01; TPC1, 94.48 vs 22.33, P=0.01). Significant changes in chemokine expression were not seen in the follicular or anaplastic thyroid cancer cell lines tested.
Conclusions: ILK has a cancer cell line-specific effect on the expression of pro-malignant chemokines, with significant decreases in RANTES, IP-10, and MIP1-alpha in the papillary thyroid cancer lines KTC1 and TPC1. This establish a new role for ILK in regulating the thyroid cancer microenvironment. Further research is needed to determine the mechanisms behind this alteration in chemokine secretion.
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Biological and Biomedical Sciences
Keywords
cancer, thyroid, chemokine