Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung cancer through cancer-derived exosomes.
Profilin 2 promotes growth, metastasis, and angiogenesis of small cell lung cancer through cancer-derived exosomes.
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DOI：
10.18632/aging.202213
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发表时间：
2020-11-21
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Cao Q;Liu Y;Wu Y;Hu C;Sun L;Wang J;Li C;Guo M;Liu X;Lv J;Huo X;Yue J;Du X;Chen Z
小细胞肺癌(SCLC)是一种高度侵袭性的肿瘤，容易发生血管过度转移。最近，我们发现Profilin 2(PFN2)在小细胞肺癌组织中表达，而在正常组织中不表达。此外，已有研究表明，PFN2的表达可通过外切体促进血管生成。然而，目前尚不清楚PFN2是否通过血管生成参与了小细胞肺癌的进展和转移。我们在这里报道了PFN2的过表达(OE)增加，而它的敲除(KD)减少了SCLC细胞H446的增殖、迁移和侵袭。OE-H446的外切体(SCLC-OE-exo)对H446的性质也有类似的影响。内皮细胞在SCLC-OE条件培养液(CM)或SCLC-OE-exo条件培养液中培养可增加内皮细胞的迁移和成管能力，而SCLC-KD-CM和SCLC-KD-exo则有抑制作用。有趣的是，SCLC和EC来源的外切体在H446中内化的速度比ECs更快。更重要的是，在肿瘤异种移植模型中，OE-PFN2显著促进了小细胞肺癌的生长和血管形成以及肺转移。最后，我们发现PFN_2在H446细胞中激活Smad2/3，在ECs中激活PERK。综上所述，我们的研究揭示了PFN2在小细胞肺癌的发生和转移中的作用，以及通过外切体促进肿瘤血管生成，为小细胞肺癌的治疗提供了一个新的分子靶点。
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.
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DOI：
10.1016/j.jtho.2016.01.012
发表时间：
2016-04
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
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发表时间：
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期刊：
Science (New York, N.Y.)
影响因子：
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