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, Gary L. Clayman

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1937-1950
Number of pages14
JournalAmerican Journal of Pathology
Volume156
Issue number6
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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