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Updated: Mar 16, 2026
A Matrigel-Based Tube Formation Assay to Assess the Vasculogenic Activity of Tumor Cells
Published on: September 7, 2011
Everolimus affects vasculogenic mimicry in renal carcinoma resistant to sunitinib
Maria Serova1,2,3, Annemilaï Tijeras-Raballand1,2,3, Celia Dos Santos1,2,3
1AAREC Filia Research, Boulogne-Billancourt, France.
Abstract:
Angiogenesis is hallmark of clear cell renal cell carcinogenesis. Anti-angiogenic therapies have been successful in improving disease outcome; however, most patients treated with anti-angiogenic agents will eventually progress. In this study we report that clear cell renal cell carcinoma was associated with vasculogenic mimicry in both mice and human with tumor cells expressing endothelial markers in the vicinity of tumor vessels. We show that vasculogenic mimicry was efficiently targeted by sunitinib but eventually associated with tumor resistance and a more aggressive phenotype both in vitro and in vivo. Re-challenging these resistant tumors in mice, we showed that second-line treatment with everolimus particularly affected vasculogenic mimicry and tumor cell differentiation compared to sorafenib and axitinib. Finally, our results highlighted the phenotypic and genotypic changes at the tumor cell and microenvironment levels during sunitinib response and progression and the subsequent improvement second-line therapies bring to the current renal cell carcinoma treatment paradigm.
Insights
Clear cell renal cell carcinoma exhibits vasculogenic mimicry, a process targeted by sunitinib. Second-line everolimus effectively combats resistance and promotes tumor cell differentiation.
Area of Science:
- Oncology
- Cancer Biology
- Renal Cell Carcinoma Research
Background:
- Angiogenesis is critical in clear cell renal cell carcinogenesis, with anti-angiogenic therapies showing initial success.
- Most patients eventually develop resistance to anti-angiogenic agents, necessitating alternative treatment strategies.
Purpose of the Study:
- To investigate the role of vasculogenic mimicry in clear cell renal cell carcinoma (ccRCC) progression.
- To evaluate the efficacy of sunitinib and subsequent second-line therapies against vasculogenic mimicry in ccRCC.
Main Methods:
- Analysis of vasculogenic mimicry in ccRCC tumor cells expressing endothelial markers in mice and humans.
- In vitro and in vivo studies assessing sunitinib efficacy and resistance.
- Comparative analysis of second-line treatments (everolimus, sorafenib, axitinib) in resistant ccRCC models.
Main Results:
- ccRCC demonstrated vasculogenic mimicry, with tumor cells expressing endothelial markers near vessels.
- Sunitinib initially targeted vasculogenic mimicry but led to resistance and a more aggressive phenotype.
- Everolimus demonstrated superior efficacy in re-challenging resistant tumors, impacting vasculogenic mimicry and tumor differentiation compared to sorafenib and axitinib.
Conclusions:
- Vasculogenic mimicry is a key mechanism in ccRCC progression and resistance to anti-angiogenic therapy.
- Understanding phenotypic and genotypic changes is crucial for optimizing treatment strategies.
- Second-line everolimus offers a promising therapeutic approach for advanced ccRCC by targeting vasculogenic mimicry and promoting differentiation.
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