Progression of malignancy in clear cell renal cell carcinomas

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Updated: Aug 23, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

I Virtanen1, V P Lehto

  • 1Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland. ismo.virtanen@helsinki.fi

Scandinavian Journal of Surgery : SJS : Official Organ for the Finnish Surgical Society and the Scandinavian Surgical Society
|August 3, 2004
PubMed

Insights

Clear cell renal cell carcinoma (CC-RCC) progression involves the von Hippel-Lindau tumor suppressor gene (VHL) inactivation. This leads to altered cell cycle, hypoxia resistance, and increased angiogenesis, promoting tumor growth and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Recent advancements in cytogenetic, gene microarray, and proteomic techniques have improved renal cell carcinoma (RCC) classification.
  • Understanding clear cell RCC (CC-RCC) malignancy progression is linked to the von Hippel-Lindau tumor suppressor gene product (VHLp).
  • VHLp inactivation is observed in the majority of CC-RCC cases.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying CC-RCC progression.
  • To connect VHLp inactivation to specific cellular changes driving malignancy.
  • To identify key molecular factors involved in RCC progression and metastasis.

Main Methods:

  • Cytogenetic analysis
  • Gene microarray techniques
  • Proteomic analysis

Main Results:

  • VHLp inactivation disrupts cell cycle control, enhances hypoxia resistance, and promotes hyperangiogenesis.
  • Overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) subunits is observed.
  • Upregulation of proinflammatory cytokines and altered cell adhesion proteins contribute to RCC progression and metastasis.

Conclusions:

  • VHLp inactivation is a critical event in CC-RCC pathogenesis.
  • Multiple molecular pathways, including angiogenesis and inflammation, are dysregulated in CC-RCC.
  • These molecular alterations drive tumor progression, metastasis, and resistance to cellular stress.

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