Reticulocalbin 1 is required for proliferation and migration of non‐small cell lung cancer cells regulated by osteoblast‐conditioned medium
| Autor: | Chun Xia, Rui Chen, Yue Wang, Yang Xu, Bing Zhang, Haijing Fu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
proliferation migration NSCLC cell medicine.disease_cause Models Biological Bone resorption Small hairpin RNA Mice Nude mouse Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans Cell Proliferation Osteoblasts biology Chemistry RCN1 Endoplasmic reticulum Calcium-Binding Proteins Osteoblast Original Articles Cell Biology Endoplasmic Reticulum Stress biology.organism_classification osteoblast‐CM respiratory tract diseases Gene Expression Regulation Neoplastic medicine.anatomical_structure Culture Media Conditioned Cancer research Molecular Medicine Original Article Female Reticulocalbin 1 ER stress Carcinogenesis Wound healing |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.17040 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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