Research Paper Volume 12, Issue 24 pp 25981—25999

Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung cancer through cancer-derived exosomes

Qi Cao1, , Yihan Liu1, , Ying Wu1, , Caijiao Hu1, , Lei Sun2, , Jinghui Wang3, , Changlong Li1, , Meng Guo1, , Xin Liu1, , Jianyi Lv1, , Xueyun Huo1, , Junming Yue4, , Xiaoyan Du1, , Zhenwen Chen1, ,

  • 1 School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China
  • 2 Department of Pathology, Shandong Chest Hospital, Shandong 250020, Jinan, China
  • 3 Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
  • 4 Center for Cancer Research, School of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA

Received: February 3, 2020       Accepted: August 19, 2020       Published: November 21, 2020      

https://doi.org/10.18632/aging.202213
How to Cite

Copyright: © 2020 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Small cell lung cancer (SCLC) is highly aggressive and prone to hypervascular metastases. Recently, we found profilin 2 (PFN2) expression in SCLC but not in normal tissues. Furthermore, PFN2 expression had been shown to promote angiogenesis through exosomes. However, it remains unclear whether PFN2 contributes to the progression and metastasis of SCLC through angiogenesis. We report here that overexpression (OE) of PFN2 increased, whereas its knockdown (KD) decreased the proliferation, migration, and invasion of SCLC cell H446. The exosomes from OE-H446 (SCLC-OE-exo) exhibited similar effects on H446 properties. Culturing of endothelial cells (ECs) in SCLC-OE conditioned medium (CM) or SCLC-OE-exo increased the migration and tube formation ability of ECs, whereas SCLC-KD-CM and SCLC-KD-exo had inhibitory effects. Interestingly, both SCLC- and EC-derived exosomes were internalized in H446 more rapidly than in ECs. More importantly, OE-PFN2 dramatically elevated SCLC growth and vasculature formation as well as lung metastasis in tumor xenograft models. Finally, we found that PFN2 activated Smad2/3 in H446 and pERK in ECs, respectively. Taken together, our study revealed the role of PFN2 in SCLC development and metastasis, as well as tumor angiogenesis through exosomes, providing a new molecular target for SCLC treatment.

Abbreviations

SCLC: Small cell lung cancer (SCLC); PFN2: profilin 2; OE: overexpression; KD: knockdown; EC: endothelial cells; CM: condition medium; HUVEC: human umbilical vein endothelial cell.