PREPARING THE TURF: Before tumor cells arrive at their metastatic destination, part of the site is readied for them. One recent study of liver metastasis in mice found that resident macrophages called Kupffer cells take up exosomes from the original tumor (1). Additionally, macrophages from the bone marrow show up upon the release of fibronectin by other liver cells called stellate cells (2). A current proposal for additional steps in metastatic niche development includes the recruitment of epithelial cells and fibroblasts, which contribute to angiogenesis, and, finally, the arrival of tumor cells themselves (3). © IKUMI KAYAMA/STUDIO KAYAMA
In 2005, David Lyden noticed something unexpected. He and his colleagues at Weill Cornell Medical College had been researching metastasis—the spread of cancer from one part of the body to another. The team had shown that bone marrow–derived cells (BMDCs) were recruited to future metastatic sites before the arrival of tumor cells, confirming that metastasis occurred after a habitable microenvironment, or “premetastatic niche,” had been prepared.1
But carefully studying images of this microenvironment in the lung tissue of mice, Lyden saw something else. Amongst the BMDCs, the micrographs showed tiny specks, far too small to be cells, gathering at the future site of metastasis. “I said, ‘What are these viruses doing here?’” recalls Lyden. “I had no idea about exosomes, microvesicles, and microparticles.”
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