Oncotarget

Research Papers:

Integrin α5 triggers the metastatic potential in renal cell carcinoma

Ines Breuksch, Franz Prosinger, Fabian Baehr, Franz-Peter Engelhardt, Heide-Katharina Bauer, Joachim W. Thüroff, Anne-Sophie Heimes, Annette Hasenburg, Dirk Prawitt and Walburgis Brenner _

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Oncotarget. 2017; 8:107530-107542. https://doi.org/10.18632/oncotarget.22501

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Abstract

Ines Breuksch1,2, Franz Prosinger1, Fabian Baehr2, Franz-Peter Engelhardt2, Heide-Katharina Bauer1, Joachim W. Thüroff2, Anne-Sophie Heimes1, Annette Hasenburg1, Dirk Prawitt3,* and Walburgis Brenner1,2,*

1Department of Gynecology, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany

2Department of Urology, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany

3Department of Pediatrics, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany

*These authors contributed equally to this work

Correspondence to:

Walburgis Brenner, email: brenner@uni-mainz.de

Keywords: integrin α5; renal cell carcinoma; metastasis; clear cell RCC; cell adhesion molecule

Received: August 16, 2017     Accepted: October 28, 2017     Published: November 18, 2017

ABSTRACT

The therapy of advanced renal cell carcinoma (RCC) is still a major challenge. To intervene therapeutically a deeper comprehension of the particular steps of metastasis is necessary. In this context membrane bound receptors like integrins play a decisive role. We analyzed the integrin α5 expression in 141 clear cell RCC patients by Western blot. Patients with RCC expressed a significant higher level of integrin α5 in tumor than in normal tissue. The integrin α5 expression correlated with tumor grade, the development of distant metastases within five years after tumor nephrectomy and reduced survival. The RCC cell lines Caki-1 and CCF-RC1, which highly express integrin α5, were treated with fibronectin in combination with or without an inhibiting anti-integrin α5 antibody. Afterwards the migration, adhesion, viability and prominent signaling molecules were analyzed. Both cell lines showed a significant reduced migration potential as well as a decreased adhesion potential to fibronectin after treatment with an integrin α5 blocking antibody. A contribution of the AKT and ERK1/2 signaling pathways could be demonstrated. The results indicate integrin α5 as a potent marker to discriminate patients’ tumor prognosis. Consequently the integrin subunit α5 can be considered as a target for individual therapy of advanced RCC.


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