Editors' ChoiceCancer

Keeping Metastasis at Bay

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Science Translational Medicine  05 Jun 2013:
Vol. 5, Issue 188, pp. 188ec94
DOI: 10.1126/scitranslmed.3006621

Whereas cancer is common on a population level, when one considers that our bodies are composed of ~10 trillion cells, it is actually an extremely rare event on a cellular level. The incidence of hyperplasia within tissues such as the breast and prostate are far higher than the actual incidence of these cancers, suggesting that the rarity of cancer is due to the presence of a suppressive microenvironment that prevents these lesions from forming tumors. What constitutes this suppressive microenvironment is largely unknown, but uncovering candidate factors could prove key to developing anticancer therapies.

To this end, Catena et al. compared the lungs of mice that had been treated with medium conditioned by either metastatic or nonmetastatic prostate cancer cells. The authors discovered that whereas both types of medium induced recruitment of leukocytes expressing Gr1, only those cells recruited by the nonmetastatic tumor cell medium expressed thrombospondin-1 (Tsp-1). Furthermore, bone marrow–derived Gr1+ cells (BMDCs) from Tsp-1–competent mice were able to halt outgrowth of injected tumor cells. Mice without Tsp-1 were unable to prevent metastasis, but this was rescued by transplanting BMDCs from Tsp-1+ donor mice.

Because of its role in inhibiting metastasis, elevating Tsp-1 expression at potential metastatic sites might be a way to translate these observations into a clinical setting. Importantly, Catena and colleagues identified a short peptide that induces Tsp-1 in bone marrow cells. Mice treated with the peptide up-regulated Tsp-1 expression, preventing injected tumor cells from forming metastatic foci as efficiently or as rapidly as mice that did not receive the peptide. Could treating asymptomatic breast or prostate cancer survivors with this peptide delay metastatic relapse? Because this is a preliminary study in mice, it is too early to say. Nevertheless, such an approach that harnesses our tissues’ natural ability to suppress tumor growth is long overdue in the clinic.

R. Catena et al., Bone marrow–derived Gr1+ cells can generate a metastasis-resistant microenvironment via secretion of thrombospondin-1. Cancer Discovery 3, 578–589 (2013). [ABSTRACT]

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