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
- 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.202213How to Cite
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.