Transcriptional targeting in renal cancer cell lines via the human CXCR4 promoter

Yosef S. Haviv, Winan J. van Houdt, Baogen Lu, David T. Curiel, Zeng B. Zhu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Metastatic renal cell carcinoma (RCC) is often resistant to standard treatment, thereby requiring new therapeutic strategies. In this regard, tumor cell migration and metastasis have recently been shown to be regulated by chemokines and their respective receptors (e.g., SDF-1α/CXCR4). In the context of RCC, up-regulation of CXCR4 expression is closely related to the development of invasive cancer. Thus, we hypothesized that the CXCR4 pathway could be exploited for RCC targeting with gene therapy vectors. In this regard, targeting adenoviral vectors to tumor cells is critically dependent on tumor-specific gene expression. Toward the end of RCC tumor targeting, we evaluated the utility of the CXCR4 promoter in an adenoviral context. First, overexpression of CXCR4 was confirmed in several RCC cell lines. Next, an adenoviral vector was constructed, whereby the human CXCR4 promoter drives the expression of a reporter gene. We tested the activity of the CXCR4 promoter in vitro and in vivo in relevant models. Our data indicate that the human CXCR4 promoter is highly active in RCC cells but not in normal human cells. Finally, biodistribution studies in mice demonstrated dramatic repression of the CXCR4 promoter in the liver but not in the kidney. In conclusion, the unique activity of the CXCR4 promoter in RCC lines and its repression in normal human cells and in the murine liver underscore its potential utility as a novel candidate for transcriptional targeting of RCC.

Original languageEnglish
Pages (from-to)687-691
Number of pages5
JournalMolecular Cancer Therapeutics
Volume3
Issue number6
StatePublished - 1 Jun 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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