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(American Journal of Pathology. 2000;156:1937-1950.)
© 2000 American Society for Investigative Pathology

Regular Articles

In Vivo Expression of the Novel CXC Chemokine BRAK in Normal and Cancerous Human Tissue

Mitchell J. Frederick^*, Ying Henderson^*, Xiaochun Xu, Michael T. Deavers, Aysegul A. Sahin, Hong Wu, Dorothy E. Lewis^§, Adel K. El-Naggar and Gary L. Clayman^*¶

From the Departments of Head and Neck Surgery,^*
Clinical Cancer Prevention,
Pathology,
and Cancer Biology,^¶
The University of Texas M. D. Anderson Cancer Center; and the Department of Immunology,^§
Baylor College of Medicine, Houston, Texas

Using differential display, we cloned a gene with reduced expression in short-term explants of head and neck squamous cell carcinoma (HNSCC) tumors compared to cultured normal oral epithelial cells. The differentially expressed gene was identical to the recently cloned CXC chemokine BRAK, which is ubiquitously expressed in normal tissue extracts but is absent from many tumor cell lines in vitro. To define the cell populations expressing BRAK in vivo, in situ mRNA hybridization was performed on normal and cancerous tissues 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 were consistently found in infiltrating inflammatory cells (with lymphocyte morphology) in nearly all cancers examined. Furthermore, BRAK expression was demonstrated in B cells and monocytes, after stimulation of peripheral blood mononuclear cells with lipopolysaccharide. This study demonstrates for the first time up-regulation of BRAK mRNA by inflammatory cells in the tumor microenvironment and lost expression from certain cancers in vivo. The data suggest that BRAK may have a role in host-tumor interactions.

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