PMID- 33234737
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20210526
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 24
DP  - 2020 Nov 21
TI  - Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung 
      cancer through cancer-derived exosomes.
PG  - 25981-25999
LID - 10.18632/aging.202213 [doi]
AB  - 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.
FAU - Cao, Qi
AU  - Cao Q
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Liu, Yihan
AU  - Liu Y
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Wu, Ying
AU  - Wu Y
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Hu, Caijiao
AU  - Hu C
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Sun, Lei
AU  - Sun L
AD  - Department of Pathology, Shandong Chest Hospital, Shandong 250020, Jinan, China.
FAU - Wang, Jinghui
AU  - Wang J
AD  - Department of Medical Oncology, Beijing Chest Hospital, Capital Medical 
      University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 
      101149, China.
FAU - Li, Changlong
AU  - Li C
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Guo, Meng
AU  - Guo M
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Liu, Xin
AU  - Liu X
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Lv, Jianyi
AU  - Lv J
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Huo, Xueyun
AU  - Huo X
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Yue, Junming
AU  - Yue J
AD  - Center for Cancer Research, School of Medicine, The University of Tennessee 
      Health Science Center, Memphis, TN 38163, USA.
FAU - Du, Xiaoyan
AU  - Du X
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
FAU - Chen, Zhenwen
AU  - Chen Z
AD  - School of Basic Medical Sciences, Capital Medical University, Beijing Key 
      Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201121
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (PFN2 protein, human)
RN  - 0 (Profilins)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Culture Media, Conditioned
MH  - Exosomes/*metabolism
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Humans
MH  - Lung Neoplasms/blood supply/*genetics/pathology
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Neovascularization, Pathologic/*genetics
MH  - Profilins/*genetics
MH  - Small Cell Lung Carcinoma/blood supply/*genetics/pathology
PMC - PMC7803489
OTO - NOTNLM
OT  - angiogenesis
OT  - exosome
OT  - metastasis
OT  - profilin 2
OT  - small cell lung cancer
COIS- CONFLICTS OF INTEREST: The authors declare that there is no conflicts of 
      interest.
EDAT- 2020/11/26 06:00
MHDA- 2021/05/27 06:00
PMCR- 2020/12/31
CRDT- 2020/11/25 05:38
PHST- 2020/02/03 00:00 [received]
PHST- 2020/08/19 00:00 [accepted]
PHST- 2020/11/26 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/11/25 05:38 [entrez]
PHST- 2020/12/31 00:00 [pmc-release]
AID - 202213 [pii]
AID - 10.18632/aging.202213 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Nov 21;12(24):25981-25999. doi: 10.18632/aging.202213. 
      Epub 2020 Nov 21.