Oncostatin M (OSM) is a protein that acts as a signaling molecule, belonging to a group of proteins called cytokines. Cytokines are small proteins secreted by various cells, including immune and non-immune cells, to facilitate communication. OSM is part of the interleukin-6 (IL-6) family of cytokines, sharing similarities with leukemia inhibitory factor (LIF). This protein plays a broad role in numerous biological processes, influencing cell behavior and tissue responses.
How OSM Functions in the Body
OSM functions as a signaling molecule, conveying messages between cells to regulate physiological processes. It binds to specific receptors on cell surfaces, typically involving a common protein called gp130 along with either the LIF receptor or the Oncostatin M receptor (OSMR). This binding initiates a cascade of internal cellular signals, such as the activation of the JAK/STAT, MAPK, and PI3K pathways, which then influence gene expression, cell growth, differentiation, and survival.
In the immune system, OSM helps regulate immune cell activity. It is produced by activated immune cells like T-cells, monocytes, and macrophages, and can influence inflammation. For instance, OSM can stimulate endothelial cells to upregulate P-selectin, a molecule that helps leukocytes adhere and move into tissues, contributing to inflammatory responses.
OSM is also involved in tissue development and repair. It plays a role in liver development and hematopoiesis, the formation of blood cells. OSM influences cellular responses to stress or injury, regulating the expression of molecules that control extracellular matrix degradation, which is important for tissue remodeling and repair.
OSM’s Involvement in Illness
Dysregulation or abnormal activity of OSM can contribute to the development and progression of various diseases. Elevated levels of OSM are observed in chronic inflammatory and autoimmune conditions. For example, in rheumatoid arthritis, increased OSM levels in synovial fluid and tissue are linked to disease activity, where OSM promotes the secretion of pro-inflammatory cytokines and enhances the invasive ability of certain joint cells.
OSM also plays a role in fibrotic conditions, which involve excessive scar tissue formation in organs. It is produced by immune cells in response to tissue injury and can promote inflammation, vascular injury, and the activation of fibroblasts, cells that produce connective tissue. High levels of OSM have been detected in various chronic inflammatory conditions characterized by fibrosis, including idiopathic pulmonary fibrosis and certain liver diseases, contributing to matrix accumulation.
In cancer, OSM can promote tumor growth, metastasis, and resistance to treatments. It has been found to be highly expressed in certain cancer cells, such as ovarian cancer cells, and can activate oncogenic pathways like JAK/STAT. Tumor-associated macrophages can also produce OSM, which then promotes the proliferation and spread of cancer cells.
Therapeutic Approaches Targeting OSM
Understanding OSM’s involvement in various diseases has led to research into potential medical treatments. One strategy involves developing drugs that directly block OSM, often using antibodies. These antibodies can bind to OSM and prevent it from interacting with its receptors, inhibiting its signaling.
Another approach focuses on targeting the OSM receptor to prevent its signaling. Human monoclonal antibodies against the extracellular part of the OSMR have been shown to disrupt OSM-induced receptor dimerization and signaling, effectively blocking OSMR-mediated pathways. These antibodies have demonstrated the ability to inhibit the growth of certain cancer cells by suppressing oncogenic signaling.
Modulating the downstream pathways activated by OSM is also an area of investigation. These therapeutic approaches hold promise for treating conditions where OSM plays a detrimental role. The aim is to develop therapies that can precisely target the OSM pathway to mitigate its harmful effects in diseases like chronic inflammation, fibrosis, and cancer.