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Lung Tumor Cell Recruitment Assay
Published on: February 26, 2019
AXL and MET receptor tyrosine kinases are essential for lung cancer metastasis
Yun Jung Choi1, Ji Hye Kim2, Jin Kyung Rho1
1Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
Abstract:
The AXL and MET receptors regulate key processes in tumor growth, metastasis, and drug resistance; thus, they have recently been implicated as promising therapeutic targets in various tumors. We investigated the metastatic potential and crosstalk between these receptors in non‑small cell lung cancer (NSCLC). We found that the treatment of NSCLC cells with hepatocyte growth factor (HGF) and growth arrest-specific 6 (Gas6), as ligands for MET and AXL, respectively, promoted their migration and invasion ability. However, treatment with inhibitors of each of these receptors significantly reduced the migratory and invasiveness of the cells, although their inhibitory rates varied according to the inhibition of each receptor. In addition, the suppression of each receptor by shRNA resulted in reduced migration and invasiveness. Notably, the suppression of AXL was more effective than the suppression of MET in the inhibition of migration and invasion. In accordance with in vitro results, when the cells were transferred via tail vein injection, AXL inhibition was more efficient in attenuating metastasis than MET inhibition. Clinically, AXL or MET expression is associated with a poor prognosis in primary tumors of NSCLC. In summary, AXL and MET can regulate tumor metastasis, but AXL was shown to be more potent than MET in lung metastasis. Thus, we conclude that AXL might be a suitable therapeutic target for the inhibition of lung metastasis.
Insights
AXL and MET receptors drive non-small cell lung cancer (NSCLC) metastasis. AXL receptor inhibition proved more effective than MET inhibition in reducing lung metastasis, suggesting AXL as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis Research
Background:
- AXL and MET receptor tyrosine kinases are crucial in tumor progression, metastasis, and drug resistance.
- These receptors are recognized as significant therapeutic targets in various cancers, including non-small cell lung cancer (NSCLC).
- Understanding the interplay between AXL and MET is vital for developing effective NSCLC treatments.
Purpose of the Study:
- To investigate the metastatic potential and functional crosstalk between AXL and MET receptors in NSCLC.
- To evaluate the efficacy of targeting AXL and MET individually and collectively in NSCLC models.
- To determine the clinical relevance of AXL and MET expression in NSCLC patient prognosis.
Main Methods:
- Treatment of NSCLC cells with ligands (HGF for MET, Gas6 for AXL) to assess migratory and invasive capabilities.
- Utilized receptor inhibitors and short hairpin RNA (shRNA) to suppress AXL and MET activity.
- In vitro assays for cell migration and invasion, followed by in vivo metastasis models (tail vein injection).
Main Results:
- HGF and Gas6 stimulation enhanced NSCLC cell migration and invasion.
- Inhibition of AXL or MET significantly reduced cell migration and invasion, with AXL suppression showing greater efficacy.
- AXL inhibition was more potent than MET inhibition in attenuating lung metastasis in vivo, correlating with poorer patient prognosis.
Conclusions:
- AXL and MET receptors play significant roles in regulating tumor metastasis in NSCLC.
- AXL demonstrates a more potent role than MET in promoting lung metastasis.
- AXL emerges as a promising and potentially more effective therapeutic target for inhibiting lung metastasis in NSCLC.
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