Effect of trachea stiffness on tumor distribution in papillary thyroid microcarcinoma

Zhang,Hua; Li,Taiyang; Du,Xilong; Li,Qihang; Huo,Bo; Jin,Rui; Li,Ping

doi:10.3892/ol.2021.12779

Effect of trachea stiffness on tumor distribution in papillary thyroid microcarcinoma

Authors:
- Hua Zhang
- Taiyang Li
- Xilong Du
- Qihang Li
- Bo Huo
- Rui Jin
- Ping Li
View Affiliations

Affiliations: Department of Maxillofacial and Ear Nose and Throat Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300020, P.R. China, Beijing Institute of Technology, School of Aerospace Engineering, Beijing 100081, P.R. China, Beijing Joy Gene Tech Co., Ltd., Beijing 100021, P.R. China
Published online on: May 7, 2021 https://doi.org/10.3892/ol.2021.12779
Article Number: 518
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Biomechanical factors play an important role in tumor distribution, epithelial‑mesenchymal transition (EMT), invasion and other important processes. Despite fewer reports investigating biomechanical function in papillary thyroid carcinoma (PTC), a large number of PTC cases are located close to the trachea and the majority of advanced cases of PTC have been associated with invasion of the trachea. However, the effect of trachea stiffness on PTC distribution and growth remains unknown. To clarify this issue, two types of PTC cells (TPC‑1 and KTC‑1) were seeded on a substrate with different stiffness to observe cell proliferation and movement. To identify the effect of trachea stiffness on the thyroid, two thyroid lobes (left and right) were evenly divided into interior (close to the trachea) and lateral (away from the trachea) parts, based on the vertical line between the trachea and thyroid lateral margin with different von Mises stress values. As PTC originates from papillary thyroid microcarcinoma (PTMC) with a maximum diameter of <1 cm, the present study selected PTMC as the study subject to reflect initial PTC distribution in the thyroid. The association between the percentage of PTMC distribution in different parts of the thyroid and von Mises stress values was analyzed. Both PTC cells exhibited stronger proliferation and mobility on the stiff substrate compared with that on the soft substrate. Furthermore, the results of finite element analysis revealed that the von Mises stress values of the interior parts of the trachea were notably higher compared with that in the lateral parts. PTMC distribution in the interior trachea was notably greater compared with that in the lateral section. There was also an observed association between von Mises stress values and PTMC distribution. In addition, the results of RNA‑sequencing and reverse transcription‑quantitative PCR demonstrated that three biomechanical genes were overexpressed in PTMC located in the interior section compared with that in adjacent normal tissue, and the related signaling pathways were also activated in these tissues. On the whole, these results indicated that trachea stiffness may supply a suitable biomechanical environment for PTMC growth, and the related biomechanical genes may serve as novel targets for PTMC diagnosis and prognostic estimation.

View Figures

View References

1	Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE and Hall DM: Molecular interactions in cancer cell metastasis. Acta Histochem. 112:3–25. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kausch I and Böhle A: Molecular aspects of bladder cancer III. Prognostic markers of bladder cancer. Eur Urol. 41:15–29. 2002. View Article : Google Scholar : PubMed/NCBI
3	Zhang R, Ma M, Dong G, Yao RR, Li JH, Zheng QD, Dong YY, Ma H, Gao DM, Cui JF, et al: Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment. Cancer Sci. 108:1778–1786. 2017. View Article : Google Scholar : PubMed/NCBI
4	Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, et al: Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 139:891–906. 2009. View Article : Google Scholar : PubMed/NCBI
5	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. Feb 4–2021.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
6	La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F and Negri E: Thyroid cancer mortality and incidence: A global overview. Int J Cancer. 136:2187–2195. 2015. View Article : Google Scholar : PubMed/NCBI
7	Liang W and Sun F: Identification of key genes of papillary thyroid cancer using integrated bioinformatics analysis. J Endocrinol Invest. 41:1237–1245. 2018. View Article : Google Scholar : PubMed/NCBI
8	Cui D, Zhao Y and Xu J: Activated CXCL5-CXCR2 axis promotes the migration, invasion and EMT of papillary thyroid carcinoma cells via modulation of β-catenin pathway. Biochimie. 148:1–11. 2018. View Article : Google Scholar : PubMed/NCBI
9	Jasim S, Baranski TJ, Teefey SA and Middleton WD: Investigating the effect of thyroid nodule location on the risk of thyroid cancer. Thyroid. 30:401–407. 2020. View Article : Google Scholar : PubMed/NCBI
10	Brauckhoff M and Dralle H: Cervicovisceral resection in invasive thyroid tumors. Chirurg. 80:88–98. 2009.(In German). View Article : Google Scholar : PubMed/NCBI
11	Machens A, Hinze R and Dralle H: Surgery on the cervicovisceral axis for invasive thyroid cancer. Langenbecks Arch Surg. 386:318–323. 2001. View Article : Google Scholar : PubMed/NCBI
12	Kim JW, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY and Kim SY: Treatment outcomes and risk factors for recurrence after definitive surgery of locally invasive well-differentiated papillary thyroid carcinoma. Thyroid. 26:262–270. 2016. View Article : Google Scholar : PubMed/NCBI
13	He S, Liu C, Li X, Ma S, Huo B and Ji B: Dissecting collective cell behavior in polarization and alignment on micropatterned substrates. Biophys J. 109:489–500. 2015. View Article : Google Scholar : PubMed/NCBI
14	Yao P and Xin WH: Experimental study on the goiter's effect on the stress relaxation of thyroid. Chin J Control Endemic Dis. 19:79–80. 2004.PubMed/NCBI
15	Trabelsi O, del Palomar AP, López-Villalobos JL, Ginel A and Doblaré M: Experimental characterization and constitutive modeling of the mechanical behavior of the human trachea. Med Eng Phys. 32:76–82. 2010. View Article : Google Scholar : PubMed/NCBI
16	Haddad RI, Nasr C, Bischoff L, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H, Goldner W, et al: NCCN guidelines insights: Thyroid carcinoma, version 2.2018. J Natl Compr Canc Netw. 16:1429–1440. 2018. View Article : Google Scholar : PubMed/NCBI
17	Cabanillas ME, McFadden DG and Durante C: Thyroid cancer. Lancet. 388:2783–2795. 2016. View Article : Google Scholar : PubMed/NCBI
18	Robinson MD, Mccarthy DJ and Smyth GK: edgeR: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 26:139–140. 2010. View Article : Google Scholar : PubMed/NCBI
19	Benjamini Y and Hochberg Y: Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Statist Soc B. 57:289–300. 1995.
20	Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, et al: The STRING database in 2011: Functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39((Database Issue)): D561–D568. 2011. View Article : Google Scholar : PubMed/NCBI
21	Adamcsek B, Palla G, Farkas IJ, Derényi I and Vicsek T: CFinder: Locating cliques and overlapping modules in biological networks. Bioinformatics. 22:1021–1023. 2006. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Peng Y, Chen Y, Qin X, Li S and Liu Y: Unveiling the mechanotransduction mechanism of substrate stiffness-modulated cancer cell motility via ROCK1 and ROCK2 differentially regulated manner. FASEB J. 33:644.42019.PubMed/NCBI
24	Liang J, Zhang XL, Yuan JW, Zhang HR, Liu D, Hao J, Ji W, Wu XZ and Chen D: Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells. Phytother Res. 33:618–630. 2019.PubMed/NCBI
25	Pardo-Pastor C, Rubio-Moscardo F, Vogel-González M, Serra SA, Afthinos A, Mrkonjic S, Destaing O, Abenza JF, Fernández-Fernández JM, Trepat X, et al: Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. Proc Natl Acad Sci USA. 115:1925–1930. 2018. View Article : Google Scholar : PubMed/NCBI
26	McKenzie AJ, Hicks SR, Svec KV, Naughton H, Edmunds ZL and Howe AK: The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation. Sci Rep. 8:72282018. View Article : Google Scholar : PubMed/NCBI
27	Woo SH, Lukacs V, de Nooij JC, Zaytseva D, Criddle CR, Francisco A, Jessell TM, Wilkinson KA and Patapoutian A: Piezo2 is the principal mechanotransduction channel for proprioception. Nat Neurosci. 18:1756–1762. 2015. View Article : Google Scholar : PubMed/NCBI
28	Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE and Patapoutian A: Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 330:55–60. 2010. View Article : Google Scholar : PubMed/NCBI
29	Ferrari LF, Bogen O, Green P and Levine JD: Contribution of Piezo2 to endothelium-dependent pain. Mol Pain. 11:652015. View Article : Google Scholar : PubMed/NCBI
30	Nonomura K, Woo SH, Chang RB, Gillich A, Qiu Z, Francisco AG, Ranade SS, Liberles SD and Patapoutian A: Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature. 541:176–181. 2017. View Article : Google Scholar : PubMed/NCBI
31	Yang H, Liu C, Zhou RM, Yao J, Li XM, Shen Y, Cheng H, Yuan J, Yan B and Jiang Q: Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability. Oncotarget. 7:44630–44643. 2016. View Article : Google Scholar : PubMed/NCBI
32	Kameda Y, Nishimaki T, Chisaka O, Iseki S and Sucov HM: Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development. J Histochem Cytochem. 55:1075–1088. 2007. View Article : Google Scholar : PubMed/NCBI
33	Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H, Ishikawa O, Katagiri T and Nakamura Y: Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 65:3092–3099. 2005. View Article : Google Scholar : PubMed/NCBI
34	Albergaria A, Resende C, Nobre AR, Ribeiro AS, Sousa B, Machado JC, Seruca R, Paredes J and Schmitt F: CCAAT/enhancer binding protein β (C/EBPβ) isoforms as transcriptional regulators of the pro-invasive CDH3/P-cadherin gene in human breast cancer cells. PLoS One. 8:e557492013. View Article : Google Scholar : PubMed/NCBI