Anti-CSF2 monoclonal antibody, clone CWE3-32D22 [Pacific Blue™]

Gliomas attract brain-resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro-invasive cells. M-CSF (macrophage colony-stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM-CSF (granulocyte-macrophage colony-stimulating factor encoded by the CSF2 gene) but not M-CSF when compared to normal astrocytes. Knockdown of GM-CSF in GL261 glioma cells strongly reduced microglia-dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1+ cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM-CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro-invasive activation in GM-CSF-depleted gliomas. Deficiency of M-CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1+ cells, but impaired accumulation of Iba1+ cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and in response to injury. The expression of CSF2 (but not CSF1) was highly up-regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM-CSF triggers and drives the alternative activation of tumour-infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Several studies have reported quantitative trait loci (QTL) for meat quality on porcine chromosome 2 (http://www.animalgenome.org/QTLdb/pig.html). For application of the molecular genetic information to the pig industry through marker-assisted selection, single nucleotide polymorphism (SNP) markers were analyzed by comparative re-sequencing of polymerase chain reaction (PCR) products of 13 candidate genes with DNA from commercial pig breeds such as Berkshire, Yorkshire, Landrace, Duroc and Korean Native pig. A total of 34 SNPs were identified in 15 PCR products producing an average of one SNP in every 253 bp. PCR restriction fragment length polymorphism (RFLP) assays were developed for I I SNPs and used to investigate allele frequencies in five commercial pig breeds in Korea. Eight of the SNPs appear to be fixed in at least one of the five pig breeds, which indicates that different selection among pig breeds might be applied to these SNPs. Polymorphisms detected in the PTH, CSF2 and FOLR genes were chosen to genotype a Berkshire-Yorkshire pig breed reference family for linkage and association analyses. Using linkage analysis, PTH and CSF2 loci were mapped to pig chromosome 2, while FOLR was mapped to pig chromosome 9. Association analyses between SNPs in the PTH, CSF2 and FOLR suggested that the CSF2 MboII polymorphism was significantly associated with several pork quality traits in the Berkshire and Yorkshire crossed F2 pigs. Our current findings provide useful SNP marker information to fine map QTL regions on pig chromosome 2 and to clarify the relevance of SNP and quantitative traits in commercial pig populations. (Key Words : Pig, Quantitative Trait Loci, Pig Chromosome 2, Single Nucleotide Polymorphism, Meat Quality)