Discovery of a new marker to identify myeloid cells associated with metastatic breast tumours

发现一种用于识别与转移性乳腺肿瘤相关的髓系细胞的新标记物

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作者:Ansooya A Bokil, Mathieu Le Boulvais Børkja, Camilla Wolowczyk, Apsana Lamsal, Wenche S Prestvik, Unni Nonstad, Kristine Pettersen, Sonja B Andersen, Anna M Bofin, Geir Bjørkøy, Sjoerd Hak, Miriam S Giambelluca

Background

Myeloid cells play an essential role in cancer metastasis. The phenotypic diversity of these cells during cancer development has attracted great interest; however, their functional heterogeneity and plasticity have limited their role as prognostic markers and therapeutic targets.

Conclusion

Our findings highlight the potential use of ARG1-positive myeloid cells as an independent prognostic marker to evaluate the risk of metastasis in breast cancer patients.

Methods

To identify markers associated with myeloid cells in metastatic tumours, we compared transcriptomic data from immune cells sorted from metastatic and non-metastatic mammary tumours grown in BALB/cJ mice. To assess the translational relevance of our in vivo findings, we assessed human breast cancer biopsies and evaluated the association between arginase 1 protein expression in breast cancer tissues with tumour characteristics and patient outcomes.

Results

Among the differentially expressed genes, arginase 1 (ARG1) showed a unique expression pattern in tumour-infiltrating myeloid cells that correlated with the metastatic capacity of the tumour. Even though ARG1-positive cells were found almost exclusively inside the metastatic tumour, ARG1 protein was also present in the plasma. In human breast cancer biopsies, the presence of ARG1-positive cells was strongly correlated with high-grade proliferating tumours, poor prognosis, and low survival.

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