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Updated: May 24, 2026

Lung Tumor Cell Recruitment Assay
Published on: February 26, 2019
Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis
Motoyoshi Endo1, Masahiro Nakano, Tsuyoshi Kadomatsu
1Department of Molecular Genetics, Kumamoto University, Kumamoto, Japan.
Abstract:
Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here, we report evidence of critical role for the angiopoietin-like protein 2 (ANGPTL2) in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In patients with lung cancer, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2, and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor cell-derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor cell-derived ANGPTL2 accelerated metastasis and shortened survival whereas attenuating ANGPTL2 expression in tumor cells-blunted metastasis and extended survival. Overall, our findings showed that tumor cell-derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process.
Insights
Angiopoietin-like protein 2 (ANGPTL2) drives cancer metastasis by increasing tumor cell motility and invasion. Inhibiting ANGPTL2 may offer a new strategy to combat metastatic disease progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastasis inhibition strategies often fail due to limited mechanistic understanding.
- Angiopoietin-like protein 2 (ANGPTL2) is implicated in inflammatory carcinogenesis in mice but its role in human tumors is unstudied.
Purpose of the Study:
- To investigate the role of ANGPTL2 in human lung cancer metastasis.
- To explore the mechanisms by which ANGPTL2 influences tumor cell behavior and metastatic potential.
Main Methods:
- Analysis of ANGPTL2 expression in human lung cancer tissues and correlation with disease-free survival.
- Investigation of transcription factors regulating ANGPTL2 expression in aggressive tumor cells.
- In vitro studies assessing the effect of tumor cell-derived ANGPTL2 on cell motility and invasion.
- Xenograft mouse models to evaluate the impact of ANGPTL2 on metastasis and survival.
Main Results:
- Elevated ANGPTL2 expression in primary lung tumors correlated with reduced disease-free survival.
- NFATc, ATF2, and c-Jun transcription factors were found to upregulate ANGPTL2 expression in aggressive tumor cells.
- Tumor cell-derived ANGPTL2 enhanced in vitro motility and invasion via autocrine/paracrine signaling.
- In vivo, ANGPTL2 accelerated metastasis and reduced survival, while its attenuation blunted metastasis and improved survival.
Conclusions:
- Tumor cell-derived ANGPTL2 is a critical driver of metastasis in lung cancer.
- Targeting ANGPTL2 represents a potential therapeutic strategy to inhibit cancer metastatic progression.
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