Reticulocalbin 1 is required for proliferation and migration of non-small cell lung cancer cells regulated by osteoblast-conditioned medium.
Reticulocalbin 1 is required for proliferation and migration of non-small cell lung cancer cells regulated by osteoblast-conditioned medium.
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DOI：
10.1111/jcmm.17040
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发表时间：
2021-12
影响因子：
5.3
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Fu H;Chen R;Wang Y;Xu Y;Xia C;Zhang B
网织红蛋白1（RCN 1）与肿瘤发生和肿瘤进展有关。然而，RCN 1是否介导非小细胞肺癌（NSCLC）细胞的骨转移尚不清楚。在此，我们评估了成骨细胞条件培养基（CM）对NSCLC细胞系NCI-H1299和NCI-H460细胞增殖和迁移的影响，并分别使用MTT、克隆形成、Transwell、伤口愈合、RT-PCR和Western印迹分析以及LC-MS/MS分析鉴定了成骨细胞和NSCLC细胞CM中的可溶性介质。此外，在有或没有成骨细胞-CM的情况下培养的NSCLC细胞中研究了RCN 1的作用。使用体内成像技术和micro-CT，在携带用shRNA/RCN 1载体转导的NCI-H1299细胞的裸鼠模型中测量肿瘤生长和骨吸收。结果显示，在成骨细胞-CM中具有较高丰度的RCN 1，其存在于细胞外囊泡（EV）中，增强了NSCLC细胞中的RCN 1表达。成骨细胞-CM部分抵消了RCN 1耗竭对NSCLC细胞增殖和迁移的抑制作用。RCN 1耗竭诱导的内质网（ER）应激（由GRP 78、CHOP、IRE 1 α、p-IRE 1 α、p-PERK和p-JNK增加引起，受自身诱导的自噬正调控）有助于抑制NCI-H1299细胞的增殖和迁移。因此，成骨细胞产生的RCN 1部分通过EV转移到NSCLC细胞中，通过阻断ER应激促进NSCLC细胞的增殖和迁移。RCN 1可能是成骨细胞-CM调控的NSCLC细胞增殖和迁移所必需的。
Reticulocalbin1 (RCN1) is implicated in tumorigenesis and tumour progression. However, whether RCN1‐mediated bone metastasis of non‐small cell lung cancer (NSCLC) cells was elusive. Here, we assessed the effect of osteoblast‐conditioned medium (CM) on proliferation and migration of NSCLC cell line, NCI‐H1299 and NCI‐H460 cells, and identified the soluble mediators in CMs from osteoblasts and NSCLC cells using MTT, Clonogenicity, Transwell, wound healing, RT‐PCR, and Western blotting assays, and LC‐MS/MS analysis, respectively. Furthermore, the role of RCN1 was investigated in NSCLC cells cultured with or without osteoblast‐CM. Tumour growth and bone resorption were measured in a nude mouse model bearing NCI‐H1299 cells transduced with shRNA/RCN1 vector using in vivo imaging technique and micro‐CT. The results showed that RCN1 with a higher abundance in osteoblast‐CM, which was present in extracellular vesicles (EVs), enhanced RCN1 expression in NSCLC cells. Osteoblast‐CM partially offset the inhibitory effect of RCN1 depletion on proliferation and migration of NSCLC cells. RCN1 depletion‐induced endoplasmic reticulum (ER) stress caused by increasing GRP78, CHOP, IRE1α, p‐IRE1α, p‐PERK and p‐JNK, which was positively regulated by self‐induced autophagy, contributed to suppression of proliferation and migration in NCI‐H1299 cells. Therefore, osteoblasts produced RCN1 to transfer into NSCLC cells partially through EVs, facilitating proliferation and migration of NSCLC cells via blocking ER stress. RCN1 could be required for proliferation and migration of NSCLC cells regulated by osteoblast‐CM.
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