Cellular and molecular life sciences : CMLS, 2021-12, Vol.78 (23), p.7709-7732
2021
Details
- Autor(en) / Beteiligte
- Titel
- GRP78 facilitates M2 macrophage polarization and tumour progression
- Ist Teil von
- Cellular and molecular life sciences : CMLS, 2021-12, Vol.78 (23), p.7709-7732
- Ort / Verlag
- Cham: Springer International Publishing
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- springer (창간호~2014)
- Beschreibungen/Notizen
- This study investigated the regulation of GRP78 in tumour-associated macrophage polarization in lung cancer. First, our results showed that GRP78 was upregulated in macrophages during M2 polarization and in a conditioned medium derived from lung cancer cells. Next, we found that knocking down GRP78 in macrophages promoted M1 differentiation and suppressed M2 polarization via the Janus kinase/signal transducer and activator of transcription signalling. Moreover, conditioned medium from GRP78- or insulin-like growth factor 1-knockdown macrophages attenuated the survival, proliferation, and migration of lung cancer cells, while conditioned medium from GRP78-overexpressing macrophages had the opposite effects. Additionally, GRP78 knockdown reduced both the secretion of insulin-like growth factor 1 and the phosphorylation of the insulin-like growth factor 1 receptor. Interestingly, insulin-like growth factor 1 neutralization downregulated GRP78 and suppressed GRP78 overexpression-induced M2 polarization. Mechanistically, insulin-like growth factor 1 treatment induced the translocation of GRP78 to the plasma membrane and promoted its association with the insulin-like growth factor 1 receptor. Finally, IGF-1 blockade and knockdown as well as GRP78 knockdown in macrophages inhibited M2 macrophage-induced survival, proliferation, and migration of lung cancer cells both in vitro and in vivo.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1420-682XeISSN: 1420-9071DOI: 10.1007/s00018-021-03997-2Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11072571
- Format
- –
- Schlagworte
- Animals, Apoptosis, Biochemistry, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Biomedical and Life Sciences, Biomedicine, Cell Biology, Cell Movement, Cell Proliferation, Cell survival, Endoplasmic Reticulum Chaperone BiP - genetics, Endoplasmic Reticulum Chaperone BiP - metabolism, Gene Expression Regulation, Neoplastic, Growth factors, Humans, Insulin, Insulin-like growth factor I, Insulin-Like Growth Factor I - genetics, Insulin-Like Growth Factor I - metabolism, Insulin-like growth factors, Janus kinase, Janus Kinases - genetics, Janus Kinases - metabolism, Kinases, Leukocyte migration, Life Sciences, Lung cancer, Lung Neoplasms - genetics, Lung Neoplasms - immunology, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Macrophage Activation, Macrophages, Macrophages - immunology, Mice, Mice, Nude, Neutralization, Original, Original Article, Phosphorylation, Polarization, Receptors, STAT1 Transcription Factor - genetics, STAT1 Transcription Factor - metabolism, Survival, Transcription, Translocation, Tumor Cells, Cultured, Tumors, Xenograft Model Antitumor Assays