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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Ror2, a Developmentally Regulated Kinase, Is Associated With Tumor Growth, Apoptosis, Migration, and Invasion in

Chun-Ming Yang1, Shan Ji, Yan Li

  • 1Department of Urology, The First Affiliated Hospital, China Medical University, Shenyang, P.R. China.

Oncology Research
|March 10, 2017
PubMed

Insights

Receptor tyrosine kinase-like orphan receptor 2 (Ror2) drives renal cell carcinoma (RCC) growth and metastasis. Inhibiting Ror2 with shRNA suppressed tumor progression and induced cancer cell death, offering a potential therapeutic target for resistant RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) is highly resistant to conventional treatments like radiation and chemotherapy.
  • Current RCC therapies are limited by a lack of effective diagnostic and therapeutic markers.
  • Tumor-associated kinases play a crucial role in regulating cancer cell behavior and tumor progression.

Purpose of the Study:

  • To investigate the role of the novel tumor-associated kinase, receptor tyrosine kinase-like orphan receptor 2 (Ror2), in renal cell carcinoma.
  • To determine if Ror2 expression correlates with specific genes involved in RCC cell cycle and migration.
  • To evaluate the therapeutic potential of targeting Ror2 in RCC.

Main Methods:

  • Investigated Ror2 expression in RCC primary tumors and cell lines.
  • Utilized short hairpin RNA (shRNA) to knockdown Ror2 expression in RCC cells.
  • Performed in vitro migration and Matrigel invasion assays.
  • Analyzed gene expression correlations (PCNA, CDK1, TWIST, MMP-2).
  • Conducted in vivo xenograft studies in nude mice using Ror2 shRNA plasmid.

Main Results:

  • Ror2 knockdown significantly reduced RCC cell proliferation and induced apoptosis.
  • Inhibition of Ror2 decreased RCC cell migration and invasive capabilities.
  • Ror2 expression in RCC correlated with genes regulating cell cycle and migration (PCNA, CDK1, TWIST, MMP-2).
  • In vivo administration of Ror2 shRNA plasmid significantly suppressed tumor growth in xenograft models.

Conclusions:

  • Ror2 acts as a novel tumor-promoting kinase in renal cell carcinoma.
  • Targeting Ror2 presents a promising therapeutic strategy for RCC.
  • Understanding the Ror2 pathway offers new insights into RCC tumorigenesis and treatment resistance.

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