Effects of stanniocalcin-1 overexpressing hepatocellular carcinoma cells on macrophage migration.

Human stanniocalcin-1 (STC1) is a glycoprotein known to participate in inflammation and tumor progression. However, its role in cancer-macrophage interaction at the tumor environment is not known. In this study, the co-culture of the human metastatic hepatocellular carcinoma cell line (MHCC97L) stably transfected with a control vector (MHCC97L/P), or STC1-overexpressing vector (MHCC97L/S1) with human leukemia monocytic cell line (THP-1) was conducted. We reported that MHCC97L/S1 suppressed the migratory activity of THP-1. Real-time PCR analysis revealed the downregulation of the pro-migratory factors, monocyte-chemoattractant protein receptors, CCR2 and CCR4, and macrophage-migratory cytokine receptor, CSF-1R. Transcriptomic analysis of the THP-1 cells co-cultured with either MHCC97L/P or MHCC97L/S1, detected 1784 differentially expressed genes. The Ingenuity Canonical Pathway analysis predicted that RhoA signaling was associated with the inhibition of the cell migration. Western blot analysis revealed a significant reduction of Ser19-phosphorylation on MLC2, a Rho-A downstream target, in the THP-1 cells. Xenograft tumors derived from MHCC97/S1 in mice showed a remarkable decrease in infiltrating macrophages. Collectively, this is the first report to demonstrate the inhibitory effect of STC1-overexpressing cancer cells on macrophage migration/infiltration. Our data support further investigations on the relationship between tumor STC1 level and macrophage infiltration.