Abstract
BackgroundOncostatin M (OSM) has been reported to be a key regulating factor in the process of tumor development. Previous studies have demonstrated both the promotion and inhibition effects of OSM in tumors, therefore inspiring controversies. However, no systematic assessment of OSM across various cancers is available, and the mechanisms behind OSM-related cancer progression remain to be elucidated.MethodsBased on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we conducted a pan-cancer analysis on OSM to explore its tumor-related functions across cancers as well as its correlations with specific molecules, cells in the tumor microenvironment. Considering the results of pan-cancer analysis, we chose the specific tumor glioblastoma multiforme (GBM) to screen out the OSM-induced signaling pathways and intercellular communications in tumor progression. Wound scratch assay, invasion assay and qRT-PCR were performed to verify the biological effects of OSM on glioblastoma cells.ResultsHigher OSM level was found in most tumor tissues compared with corresponding normal tissues, and the enhanced OSM expression was observed to be strongly related to patients’ poor prognosis in several cancers. Moreover, the expression of OSM was associated with stromal and immune cell infiltration in the tumor microenvironment, and OSM-related immune checkpoint and chemokine co-expression were also observed. Our results suggested that OSM could communicate extensively with the tumor microenvironment. Taking GBM as an example, our study found that two critical signaling pathways in OSM-related tumor progression by KEGG enrichment analysis: Jak-STAT and NF-κB pathways. Single-cell RNA sequencing data analysis of GBM revealed that OSM was mainly secreted by microglia, and cell–cell interaction analysis proved that OSM-OSMR is an important pathway for OSM to stimulate malignant cells. In vitro, OSM treatment could facilitate the migration and invasion of glioblastoma cells, meanwhile promote the proneural-mesenchymal transition. The administration of STAT3 inhibitors effectively suppressed the OSM-mediated biological effects, which proved the key role of STAT3 in OSM signaling.ConclusionTaken together, our study provides a comprehensive understanding with regard to the tumor progression under the regulation of OSM. OSM seems to be closely related to chronic inflammation and tumor development in the tumor microenvironment. As an important inflammatory factor in the tumor microenvironment, OSM may serve as a potential immunotherapeutic target for cancer treatment, especially for GBM.
Highlights
Oncostatin M (OSM) has been reported to be a key regulating factor in the process of tumor development
OSM expression in normal and tumor tissues across pan‐cancer Our study aims to probe into the expression of OSM in normal controls and tumor tissues across multiple cancer types
We downloaded the data of each tumor cell line from the Cell Line Encyclopedia (CCLE) database, and analyzed the OSM expression level in 21 tissues which were divided according to the tissue source (Fig. 1b)
Summary
Oncostatin M (OSM) has been reported to be a key regulating factor in the process of tumor development. Previous studies have demonstrated both the promotion and inhibition effects of OSM in tumors, inspiring controversies. Oncostatin M (OSM), a member of the IL-6 family, has been considered an important cytokine in diverse physiological and pathological processes. Our previous study indicated that OSM was highly expressed in jaw bone marrow, serving as an important inflammatory factor that regulated the homeostasis of jaw bone [5]. Some studies deeply demonstrated that the inhibitory effects of OSM in cancers were mainly associated with the deceleration of tumor cell proliferation and the promotion of cell differentiation rather than cell apoptosis or cell death [7, 8]. A large number of studies describe its specific roles across various cancers, there is still a lack of systematic studies to determine the role of OSM across various cancer types
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