Osteopontin is involved in TLR4 pathway contributing to ovarian cancer cell proliferation and metastasis

Abstract

Tumor cell proliferation and metastasis are critical for tumor progression and lead to death of cancer patients. TLR4 is a member of the toll-like receptor (TLR) family, which promotes tumor growth, metastasis and immune escape. Osteopontin (OPN), a phosphorylated glycoprotein extensively expressed in multiple cell-types, plays important roles in tumorigenesis, metastasis and infiltration, and participates in signal transduction of innate immunity. However, it is unclear whether TLR4 has any relationship with OPN. The current study investigated the role of TLR4 and OPN in tumor proliferation and metastasis, and the potential effect of TLR4 signaling on OPN using the human ovarian cancer cell line HO-8910PM. High expression levels of TLR4 and OPN were detected in HO-8910PM cells, which promoted the proliferation, migration and invasion of tumor cells. Lipopolysaccharide (LPS) induced activation of TLR4 up-regulated OPN, increasing the malignant phenotype of cells. RNAi-mediated knockdown of OPN reduced significantly the metastatic phenotype activated by TLR4. Taken together, our study demonstrates that OPN contributes to the ovarian cancer cell proliferation and metastasis, which is activated by TLR4 signaling pathway. It provides new insights for the mechanisms of tumor development and metastasis, and suggests targeting TLR4 and OPN as an intervention in the ovarian cancer treatment.