[12] The phosphorylation allows SHP1 or SHP2 recruitment to SIRPα that, in turn, dephosphorylates specific substrates involved in various physiological effects.[14, 15] SIRPα can bind to either widely expressed transmembrane Adriamycin mouse ligand CD47 or soluble ligands, such as the surfactant proteins A and D.[16] It is suggested that the SIRPα/CD47 signaling axis is important in tumor therapy.[17, 18] Our previous work has shown that SIRPα negatively regulate Toll-like receptor (TLR) signaling in Mψ.[16, 19] However, it is still unknown whether SIRPα expression on tumor-polarized

Mψ can act on tumor progression. We demonstrate here that SIRPα expression is reduced on Mψ obtained from peritumoral tissues of HCC patients. Down-regulated SIRPα expression is coincident with transiently activated Mψ during the early stage of exposure to tumor. Moreover, adoptive transfer of SIRPα-KD Mψ could promote tumor growth in vivo. These findings provide a new role of SIRPα on tumor-polarized Mψ and tumor progression. Peripheral blood samples of healthy donors (n = 20) and untreated BGJ398 research buy HCC patients (n = 22) as well as HCC tumor samples (n = 25) were obtained. Tumor tissues were collected from the areas of tumor nest, while the peritumoral samples were obtained near the tumor tissues (0.5-1 cm from tumor margin). The patients were pathologically confirmed

as HCC at the Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Detailed information about the patients and their tumors are shown

in Supporting Table. 1. Written informed consent was obtained and the protocols were approved by the Review Board of the Eastern Hepatobiliary Surgery Hospital. The circulating mononuclear cells were obtained by Ficoll density gradient centrifugation. selleckchem The infiltrated leukocytes were isolated according to the following protocols: specimens were cut into small pieces and digested with 0.05% collagenase IV, 0.002% DNase I (Sigma-Aldrich), and 20% fetal bovine serum (FBS) (Gibco) at 37°C for 1 hour. The dissociated cells were filtered through 150-μm mesh and separated by Percoll centrifugation. The obtained cells were washed for the fluorescent-activated cell sorter (FACS) analysis. Male C57BL/6 mice and Balb/c mice (6-8 weeks old) were obtained from the Chinese Science Academy, Shanghai, China, and maintained under pathogen-free conditions. All animals received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals, prepared by the National Institutes of Health. Experiments were performed repeatedly and representative data are shown. Continuous variables were compared with the Student t test, ordinal variables with the Mann-Whitney U test. P 0.05 was considered significant. Data analysis was performed with SPSS 16.0 for Windows (Chicago, IL). A detailed description of Patients and Methods can be found in the online Supporting Information.