Thrombin Cleavage of Osteopontin and the Host Anti-Tumor Immune Response

SIMPLE SUMMARY: Osteopontin (OPN) is a protein produced by immune cells, as well as many other cell types including tumor cells, that is highly modified with sugars and phosphates. OPN binds to receptors present on many cell types including cancer and immune cells and causes those cells to change properties. OPN is increased in the blood of cancer patients. OPN can be cut by thrombin, the major enzyme responsible for blood clotting, into two fragments that have different properties from intact OPN. These fragments suppress the host’s immune response to cancer, allowing the cancer to grow faster and to metastasize. ABSTRACT: Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. Thrombin cleavage of OPN initiates OPN’s tumor-promoting activity, and thrombin cleavage fragments of OPN down-regulate the host immune anti-tumor response.