Targeting syndecan-2 inhibits papillary thyroid cancer invasiveness and de-differentiation

The high incidence of recurrence and metastatic disease remain the major issues for papillary thyroid cancer (PTC) patients. Previous studies have demonstrated that Syndecan-2 (SDC2) plays a key role in multiple cancers progression. However, the potential role of SDC2 in PTC progression and recurrence remains unclear.

First, we performed bioinformatics analysis and western-blotting analysis to explore the potential prognostic value of SDC2 in PTC. Then we applied transient siRNA knockdown and plasmid overexpression to alter SDC2 expression level in PTC cell line B-CPAP and KTC-1. After that, we carried out scratch wound healing assay, transwell assay and cell counting kits-8 (CCK8) assay to explore the cell migration, invasiveness and viability. We also explored expressions of mesenchymal and epithelial markers, multiple thyroids differentiating markers and hedgehog signaling members to address the potential underlying mechanisms.

Firstly, we found a significant negative correlation of SDC2 expression with advanced disease characters in PTC. Then bioinformatic analysis indicated the SDC2 expression was closely related to multiple key pathways and thyroid differentiation markers. Targeting SDC2 expression significantly influenced the growth and invasion of PTC cells according to series of assays. Western-blotting results of α-SMA and ZO-1 also indicated the altered EMT process. Furthermore, attenuated SDC2 expression also leads to the PTC de-differentiation, which could be due to hedgehog signaling alteration.

Our findings suggest that SDC2 would be a promising therapy target for advanced radioiodine refractory thyroid cancer, but the role in PTC progression is complicated and requires further exploration.