In vivo expression of the novel CXC chemokine BRAK in normal and canceroushuman tissue

Using differential display, we cloned a gene with reduced expression in sho rt-term explants of head and neck squamous cell carcinoma (HNSCC) tumors co m pared to cultured normal oral epithelial cells. The differentially expres sed gene was identical to the recently cloned CXC chemokine BRAK, which is ubiquitously expressed in normal tissue extracts but is absent from many tu mor cell lines in vitro, To define the cell populations expressing BRAK in vivo, in situ mRNA hybridization was performed on normal and cancerous tiss ues from six different histological sites. The predominant normal cell type constitutively expressing BRAK in vivo was squamous epithelium, Expression in tumors was heterogeneous, with the majority of HNSCCs and some cervical squamous cell carcinomas (SCCs) showing loss of BRAK mRNA. Although absent in unstimulated peripheral blood mononuclear cells, high levels of BRAK we re consistently found in infiltrating inflammatory cells (with lymphocyte m orphology) in nearly all cancers examined. Furthermore, BRAK expression was demonstrated in B cells and monocytes, after stimulation of peripheral blo od mononuclear cells with lipopolysaccharide. This study demonstrates for t he first time up-regulation of BRAK mRNA by inflammatory cells in the tumor microenvironment and lost expression from certain cancers in vivo. The dat a suggest that BRAK may have a role in host-tumor interactions.