Osteopontin, encoded by SPP1, is a secreted extracellular matrix glycoprotein recognized by several cell surface receptors, including CD44 and the alpha-v-beta-3 integrin. It is highly expressed by bone-resident cells and promotes osteoclast adhesion to bone matrix.
In cancer it has long been associated with bone-seeking (osteotropic) metastasis: it promotes cancer cell adhesion and migration in mouse models, and high SPP1 expression in patients is a feature of bone metastasis and an indicator of its prevalence. Certain transformed cell types also induce osteopontin in response to substrate stiffness and on entry into the bone microenvironment.
Its effects on immunity are not one-directional. Osteopontin can inhibit cytotoxic T lymphocyte activation by engaging CD44, a receptor expressed on both T cells and NK cells, which makes it a complicated therapeutic target.
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Source papers
- Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells doi:10.1016/j.immuni.2026.06.025