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VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell carcinoma

  1. Jacqueline Rivet MD1,
  2. Samia Mourah MD, PhD2,
  3. Hideyuki Murata MD, PhD1,
  4. Nicolas Mounier MD, PhD1,
  5. Helena Pisonero1,
  6. Pierre Mongiat-Artus MD, PhD3,
  7. Pierre Teillac MD, PhD3,
  8. Fabien Calvo MD, PhD2,
  9. Anne Janin MD, PhD1,
  10. Christine Dosquet MD, PhD4,†,*

Article first published online: 26 NOV 2007

DOI: 10.1002/cncr.23186

Issue

Cancer

Cancer

Volume 112, Issue 2, pages 433–442, 15 January 2008

Additional Information

How to Cite

Rivet, J., Mourah, S., Murata, H., Mounier, N., Pisonero, H., Mongiat-Artus, P., Teillac, P., Calvo, F., Janin, A. and Dosquet, C. (2008), VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell carcinoma. Cancer, 112: 433–442. doi: 10.1002/cncr.23186

Author Information

  1. 1

    Laboratoire de Pathologie and U728, INSERM, Université Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie, Paris, France

  2. 2

    Laboratoire de Pharmacologie and U716, INSERM, Université Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie, Paris, France

  3. 3

    Service d'Urologie, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie, Paris, France

  4. 4

    Unité de Thérapie cellulaire and U553, INSERM, Université Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie, Paris, France

  1. †

    Fax: (011) 33 1 42 49 95 65.

*Unité de Thérapie Cellulaire, Hôpital St.-Louis, 1 avenue Claude Vellefaux 75475 Paris cedex 10 France

Publication History

  1. Issue published online: 4 JAN 2008
  2. Article first published online: 26 NOV 2007
  3. Manuscript Accepted: 9 AUG 2007
  4. Manuscript Revised: 3 AUG 2007
  5. Manuscript Received: 23 APR 2007

Funded by

  • University Paris 7
  • Inserm
  • GIP/HMR
  • PHRC

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Keywords:

  • laser microdissection;
  • renal cell carcinoma;
  • VEGF;
  • VEGFR-1;
  • VEGFR-2

Abstract

BACKGROUND.

Tumor angiogenesis is a dynamic process that plays a major role in cancer progression. Vascular endothelial growth factor (VEGF) and its receptors play a pivotal role in angiogenesis. The expression of VEGF and its receptors VEGFR-1 and VEGFR-2 in renal cell carcinoma (RCC) was investigated in the perspective of anti-VEGF treatments.

METHODS.

Total VEGF protein levels were quantified by enzyme-linked immunosorbent assay (ELISA) in tumor tissue samples from surgical specimens of 65 patients with clear cell RCC. At the cellular level the VEGF isoforms VEGFR-1 and VEGFR-2 mRNA were quantified by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in laser-microdissected tumoral epithelial as stromal cells and in corresponding normal tissue compartments. Colocalization of VEGF and VEGFR-1 proteins was studied by triple immunofluorescent labeling.

RESULTS.

Protein VEGF in cytosolic extracts was significantly higher in tumoral than in nontumoral tissue (P < .0001). Event-free survival was significantly longer for patients with cytosolic VEGF lower than the cutoff (75th percentile of VEGF protein levels, P = .02). In laser-microdissected epithelial cells, VEGF121 and VEGFR-1 mRNA expressions were higher in RCC than in corresponding nontumoral kidney (P = .007 and P = .002, respectively); they were also higher in stromal cells of RCC compared with nontumoral kidney (P = .02 and P = .003, respectively). There was no differential VEGFR-2 expression in epithelial or in stromal cells of tumoral or nontumoral kidney. By immunofluorescent labeling VEGF and VEGFR-1 colocalized on RCC tumor epithelial and stromal cells.

CONCLUSIONS.

Combined laser microdissection and quantitative RT-PCR, as triple immunofluorescent labeling, underlined the preferential expression of the most soluble VEGF isoform, VEGF121, and its receptor VEGFR-1, but not VEGFR-2, in epithelial and stromal cells of RCC. Cancer 2008. © 2007 American Cancer Society.

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