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Thymosin β15 is the only β-thymosin possessing an amino acid substitution within the expected actin binding domain, LKKTNT instead of LKKTET. Thymosin β15 is increased in prostate cancer and is reported to be important in cell migration. It is possible that thymosin β15 acts not only by increasing cell migration but also by increasing angiogenesis, which would contribute to the malignant potential of these tumor cells. Other investigators have shown that thymosin β4 levels are elevated in metastatic lesions (36ñ38) and, when transfected into tumor cells, malignancy in vitro and in vivo is increased. Furthermore, the sulfoxide of thymosin β4 has been described to possess anti-inflammatory activity (40). It likely acts in malignancy to increase migration, angiogenesis, and reduce immune surveillance.
The purpose of this study was to define the inhibitive effects of dietary nickel chloride (NiCl2) on thymocytes in broilers fed on diets supplemented with 0, 300, 600, and 900 mg/kg of NiCl2 for 42 days. We examined the changes of cell cycle phase, percentages of apoptotic cells, T cell subsets, cytokines, and mRNA expression of apoptotic proteins (bcl-2, bax, and caspase-3) in thymocytes by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). In the NiCl2-treated broilers, the percentages of thymocytes in G0/G1 phase were increased, whereas thymocytes in the S phase and the proliferation index were decreased. The percentages of apoptotic thymocytes were increased. Also, the mRNA expression levels of bax and caspase-3 were increased, and mRNA expression levels of bcl-2 were decreased. The percentages of CD3(+), CD3(+)CD4(+), and CD3(+)CD8(+) T lymphocytes in the thymus and peripheral blood were diminished. Concurrently, thymic cytokine (interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-10 (IL-10), interleukin-12 p35 subunit (IL-12p35), interleukin-12 p40 subunit (IL-12p40), interleukin-21 (IL-21), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), thymosin β4, thymosin β10, and thymosin β15) mRNA expression levels were decreased. The abovementioned results showed that dietary NiCl2 in excess of 300 mg/kg inhibited thymocyte growth by arresting cell cycle, increasing apoptosis percentage, altering apoptotic protein mRNA expression levels, and downregulating cytokine expression levels.
Tang, K., Guo, H., Deng, J., Cui, H., Peng, X., Fang, J., ... & Yin, S. (2015). Inhibitive effects of nickel chloride (NiCl2) on thymocytes. Biological trace element research, 164(2), 242-252.
Motile cancer cells depend on assembly and disassembly of actin filaments to extend their leading edges as they move, so alterations in the expression or properties of actin binding proteins may influence their invasiveness. Tumor cell movements might be enhanced by overexpression or activating mutations of proteins that stimulate the actin system or lower expression or inactivation of proteins that act as negative regulators of the actin system. Some transformed cells express reduced levels of tropomyosin or α-actinin, proteins that stabilize actin filaments and actin filament bundles, and restoring their expression can reverse some transformed phenotypes. On the other hand, the increased expression of thymosin β15 and gelsolin, proteins implicated in the disassembly of the actin filaments, correlates with poor clinical outcome of cancer patients.
Maul, R. S., Song, Y., Amann, K. J., Gerbin, S. C., Pollard, T. D., & Chang, D. D. (2003). EPLIN regulates actin dynamics by cross-linking and stabilizing filaments. J Cell Biol, 160(3), 399-407.