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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma
11] Xiangya Hospital, Central South University, Changsha, Hunan 410008, People's Republic of China [2] Department of Medicine, University of Southern California, Norris Hospital, NOR 6332, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Background:
Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC).
Methods:
Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft.
Results:
We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis.
Conclusions:
Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.
Insights
Axl receptor tyrosine kinase is highly expressed in renal cell carcinoma (RCC) and promotes tumor cell survival. Targeting Axl with antibody hMAb173 significantly inhibited RCC tumor growth and induced apoptosis, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Axl receptor tyrosine kinase is implicated in tumorigenesis across various cancers.
- Its role in renal cell carcinoma (RCC) requires further investigation.
Purpose of the Study:
- To evaluate the expression and biological function of Axl in renal cell carcinoma (RCC).
- To assess the therapeutic potential of targeting Axl in RCC.
Main Methods:
- Immunohistochemistry and western blot analysis of Axl expression in 174 RCC samples and 11 normal-tumour pairs.
- Quantitative PCR and western blot for Axl in RCC cell lines.
- Axl knockdown experiments and in vivo efficacy studies of anti-Axl antibody hMAb173.
Main Results:
- Axl is overexpressed in 59% of RCC tissues compared to normal kidney tissue.
- Axl knockdown reduced RCC cell viability and inhibited PI3K/Akt signaling.
- Anti-Axl antibody hMAb173 inhibited RCC tumor growth by 78% in vivo, inducing apoptosis and suppressing PI3K signaling.
Conclusions:
- Axl is highly expressed in RCC and essential for tumor cell survival.
- Targeting Axl represents a promising therapeutic strategy for RCC treatment.
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