Metastasis triggered by macrophage cytoplasm

Macrophages are the first line of defense against infections, playing important roles in consuming pathogens and in regulating inflammation. In general, these functions help maintain a healthy organism, keeping infections at bay and promoting healing. However, it is now well known that inflammation is associated with cancer progression, and that the presence of macrophages within a tumor often correlates with poor prognosis¹. But, the relationship between inflammation and cancer progression is poorly understood, and much is still unknown about how macrophages may contribute to tumor growth or metastasis.

Using in vivo animal models of melanoma invasion, a new study has uncovered a surprising way that macrophages may be affecting cancer cells. Using zebrafish and mouse models, high-resolution imaging, and an elegant Cre/Lox fluorescent reporter strategy, Roh-Johnson et al. discovered that macrophages actually exchange cytoplasm with melanoma cells in live animals². They observed that the presence of macrophage cytoplasm in cancer cells correlates with melanoma invasion, suggesting that cytoplasmic factors within macrophages may activate the metastatic phenotype in cancer cells.

A prior study used a similar LoxP-STOP-LoxP strategy to show that metastatic tumors can secrete vesicles which transfer cancer cell cytoplasm and migratory phenotypes into other cells in the environment³. However, macrophages have not previously been observed to transfer cytoplasm to other cells. Models for how macrophages influence cancer metastasis have generally been focused on extracellular signaling and the regulation of the tumor microenvironment. This new study fundamentally alters not only our understanding of cancer metastasis, but also our understanding of macrophage behavior. It also highlights the surprising variety of ways that cells can interact and communicate with one another.

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References

1. Rhee I. Diverse macrophages polarization in tumor microenvironment. Arch Pharm Res. 2016 Nov;39(11):1588-1596.
2. Roh-Johnson M, Shah AN, Stonick JA, Poudel KR, Kargl J, Yang GH, di Martino J, Hernandez RE, Gast CE, Zarour LR, Antoku S, Houghton AM, Bravo-Cordero JJ, Wong MH, Condeelis J, Moens CB. Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo. Dev Cell. 2017 Dec 4;43(5):549-562.e6.
3. Zomer A, Maynard C, Verweij FJ, Kamermans A, Schäfer R, Beerling E, Schiffelers RM, de Wit E, Berenguer J, Ellenbroek SIJ, Wurdinger T, Pegtel DM, van Rheenen J. In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell. 2015 May 21;161(5):1046-1057.