Role and Mechanism of TGF β1 in Platelet Promoting Invasion and Migration of Anaplastic Thyroid Carcinoma Cells
-
摘要:
目的 探索肿瘤患者血小板（platelet，PLT）是否通过分泌转化生长因子β1（transforming growth factor β1，TGFβ1）参与调控甲状腺未分化癌（anaplastic thyroid carcinoma，ATC）的转移。 方法 通过ELISA和Real-time PCR实验测定ATC细胞上清TGFβ1蛋白和mRNA表达情况；通过Transwell迁移实验、划痕实验和Western Blot方法探究TGFβ1对ATC细胞迁移及侵袭能力的影响及其作用机制。 结果 PLT与ATC细胞共培养上清液中TGFβ1蛋白水平显著上调（P < 0.001）而mRNA水平不变；PLT或rhTGFβ1可使穿过小室的ATC细胞显著增加（P < 0.001），提示PLT或rhTGFβ1能显著增强ATC细胞的迁移能力（P < 0.001）；划痕实验也证实rhTGFβ1可显著增强ATC细胞的迁移能力（P < 0.001）。 结论 PLT可通过分泌TGFβ1诱导ATC细胞EMT进程最终增强ATC细胞迁移和侵袭能力，表明TGFβ1可能成为ATC患者靶向治疗的潜在靶标。 Abstract:Objective This study aims to explore whether platelet （PLT） is involved in regulating the progression of anaplastic thyroid carcinoma （ATC） by secreting transforming growth factor β1 （TGFβ1）. Methods The levels of TGFβ1 protein and mRNA in the supernatant of ATC cells were detected by ELISA and Real-time PCR, respectively. Transwell, scratch wound test and Western Blot were used to analyze the effects of TGFβ1 on the invasive and migratory abilities of ATC cell lines and its mechanism. Results In the co-culture supernatant of PLT and ATC cells, the protein level of TGFβ1 was significantly up-regulated, but the mRNA level was unchanged. PLT or rhTGF-β1 significantly increased the number of ATC cells crossing the chamber （P < 0.001）, suggesting that PLT or rhTGF-β1 could significantly enhance the migration ability of ATC cells. Scratch wound assay also confirmed that rhTGF-β1 could significantly enhance the migration ability of ATC cells. Conclusion PLT can significantly promote the development of EMT in ATC cells by secreting TGFβ1, and then promote the invasion and migration of ATC cells, suggesting that TGFβ1 may be a potential target of ATC molecular targeted therapy. -
图 1 PLT诱导ATC细胞发生EMT
A：PLT诱导ATC细胞发生EMT样变化（×100）；B：Western blot检测EMT相关标记蛋白。
Figure 1. Platelets induce epithelial mesenchymal transition in ATC cells
图 2 PLT与ATC细胞共培养后TGFβ1 的表达情况
A：TGFβ1的mRNA表达；B：TGFβ1的蛋白表达。**P < 0.01；***P < 0.001。
Figure 2. Expression of TGFβ1 after co-culture PLT and ATC cells
图 3 rhTGFβ1促进SW579细胞迁移能力增强
A：Transwell实验提示PLT或rhTGFβ1可使SW579细胞迁移能力显著增强；B：划痕实验提示rhTGFβ1可使SW579细胞迁移能力显著增强（×100）。**P < 0.01，***P < 0.001。
Figure 3. rhTGFβ1 promotes the migratory ability of SW579 cells
-
[1] Wang X M,Peng W,Li C,et al. Identification of an immune-related signature indicating the dedifferentiation of thyroid cells[J]. Cancer Cell Int,2021,21(1):231. doi: 10.1186/s12935-021-01939-3 [2] Tiedje V,Stuschke M,Weber F,et al. Anaplastic thyroid carcinoma:Review of treatment protocols[J]. Endocr Relat Cancer,2018,25(3):R153-R161. doi: 10.1530/ERC-17-0435 [3] Buergy D,Wenz F,Groden C,et al. Tumor-platelet interaction in solid tumors[J]. Int J Cancer,2012,130(12):2747-2760. doi: 10.1002/ijc.27441 [4] Palacios-Acedo A L,Mège D,Crescence L,et al. Platelets,thrombo-inflammation,and cancer:Collaborating with the enemy[J]. Front Immunol,2019,10:1805. doi: 10.3389/fimmu.2019.01805 [5] Rothwell P M,Wilson M,Price J F,et al. Effect of daily aspirin on risk of cancer metastasis:A study of incident cancers during randomised controlled trials[J]. Lancet,2012,379(9826):1591-1601. doi: 10.1016/S0140-6736(12)60209-8 [6] Haemmerle M,Stone R L,Menter D G,et al. The platelet lifeline to cancer:Challenges and opportunities[J]. Cancer Cell,2018,33(6):965-983. doi: 10.1016/j.ccell.2018.03.002 [7] Schlesinger M. Role of platelets and platelet receptors in cancer metastasis[J]. J Hematol Oncol,2018,11(1):125. doi: 10.1186/s13045-018-0669-2 [8] Xu X R,Yousef G M,Ni H. Cancer and platelet crosstalk:Opportunities and challenges for aspirin and other antiplatelet agents[J]. Blood,2018,131(16):1777-1789. doi: 10.1182/blood-2017-05-743187 [9] Leblanc R,Peyruchaud O. Metastasis:New functional implications of platelets and megakaryocytes[J]. Blood,2016,128(1):24-31. doi: 10.1182/blood-2016-01-636399 [10] Takemoto A,Takagi S,Ukaji T,et al. Targeting podoplanin for the treatment of osteosarcoma[J]. Clin Cancer Res,2022,28(12):2633-2645. doi: 10.1158/1078-0432.CCR-21-4509 [11] Suzuki-Inoue K. Platelets and cancer-associated thrombosis:Focusing on the platelet activation receptor CLEC-2 and podoplanin[J]. Blood,2019,134(22):1912-1918. doi: 10.1182/blood.2019001388 [12] Shang Y,Sun J,Wu X,et al. Activated platelet membrane nanovesicles recruit neutrophils to exert the antitumor efficiency[J]. Front Chem,2022,10:955995. doi: 10.3389/fchem.2022.955995 [13] Li Q,Mo W,Ding Y,et al. Study of lncRNA TPA in promoting invasion and metastasis of breast cancer mediated by TGF-β signaling pathway[J]. Front Cell Dev Biol,2021,9:688751. doi: 10.3389/fcell.2021.688751 [14] Li Y,Zhou X,Liu J,et al. Dihydroartemisinin inhibits the tumorigenesis and metastasis of breast cancer via downregulating CIZ1 expression associated with TGF-β1 signaling[J]. Life Sci,2020,248:117454. doi: 10.1016/j.lfs.2020.117454 [15] Ren Y,Jia H H,Xu YQ,et al. Paracrine and epigenetic control of CAF-induced metastasis:The role of HOTAIR stimulated by TGF-ß1 secretion[J]. Mol Cancer,2018,17(1):5. doi: 10.1186/s12943-018-0758-4 -
下载:
点击查看大图
图(4)
计量
- 文章访问数: 3041
- HTML全文浏览量: 1870
- PDF下载量: 16
- 被引次数: 0
