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Published on: August 23, 2019
Tumor-Derived Exosomal PDLIM1 Promotes Angiogenesis and Tumor Progression in Papillary Thyroid Carcinoma: Insights
Wangwang Qiu1, Ting Yan1,2, Xinyu Huang1
1Department of General Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People's Republic of China.
Background:
Papillary thyroid carcinoma (PTC) with metastatic potential presents a complex and poorly understood tumor microenvironment. Despite its clinical significance, the cellular and molecular mechanisms driving metastatic progression remain inadequately characterized, particularly the role of intercellular communication mediated by tumor-derived exosomes.
Methods:
We analyzed single-cell RNA sequencing (scRNA-seq) on primary and metastatic PTC tissues (n=12 samples from 4 patients), exploring cellular heterogeneity and distinct subpopulations. Metastasis-associated cell states (Scissor+ and Scissor-) were delineated using the Scissor algorithm. Pathway activity in these subpopulations was analyzed using the PROGENy algorithm.Exosomal proteomic data from lymph node metastasis patients were cross-referenced with Scissor+ signatures, identifying candidate proteins. Functional validation included in vitro angiogenesis assays with HUVECs and in vivo xenograft models to assess tumor growth and vascularization.
Results:
ScRNA-seq revealed significant tumor cell heterogeneity between primary and metastatic sites, with Scissor+ cells strongly linked to metastatic phenotypes. PROGENy analysis demonstrated significant upregulation of VEGF signaling in Scissor+ cells. Among six key proteins identified, PDLIM1 was highly expressed in PTC cell lines and metastatic tissues (P < 0.001). Tumor-derived exosomal PDLIM1 was internalized by endothelial cells, enhancing angiogenesis in vitro. PDLIM1 knockdown in exosomes suppressed HUVEC tube formation (P < 0.05) and reduced tumor volume, CD31+ microvessel density, and LYVE-1+ lymphatic vessel density in xenografts (P < 0.05).
Conclusion:
Our study suggests that exosomal PDLIM1 may play a role in promoting angiogenesis and primary tumor progression in PTC. These findings provide preliminary insights into the potential involvement of exosome-mediated intercellular communication in PTC pathogenesis. Further validation in larger cohorts and functional studies, including rescue experiments, are warranted to evaluate whether targeting PDLIM1 could represent a viable therapeutic strategy.
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