Effect of trachea stiffness on tumor distribution in papillary thyroid microcarcinoma

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.