OPN is an integrin-binding glycoprotein also
known as secreted phosphoprotein 1 (SPP1). OPN is so named because it was first
discovered in osteoblasts and osteoclasts. The latter is developed from the
macrophage lineage. OPN protein has a secreted form and an intracellular form.
The secreted OPN has two integrin-binding domains which can adhere to integrins
on the surfaces of macrophages, making it a potent chemoattractant as well as an
activator of macrophages. In innate immunological cells such as dendritic
cells, OPN can be activated upon infection. The OPN-integrin binding can
trigger downstream macrophage activities including TNF secretion, producing an
inflammatory microenvironment. Poor prognosis of HCC was correlated with
elevated OPN RNA, tissue OPN protein levels and pre-operative serum OPN protein
levels. An anti-OPN antibody has been shown to defer the growth and metastasis
of breast cancer in a mice model. As macrophages can also secret OPN, PTM and
OPN form a vicious autocrine/paracrine cycle for the progression of cancer.
Thus, in the future, novel strategies to break this cycle could bring to new
anti-HCC treatments.
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