Editors' ChoiceCancer

Round-Trip Ticket for Circulating Tumor Cells

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Science Translational Medicine  20 Jan 2010:
Vol. 2, Issue 15, pp. 15ec11
DOI: 10.1126/scitranslmed.3000835

A tumor is found within the breast. It is excised with wide margins. Yet, the patient remains at high risk for local or distant relapse. Why?

It has been a longstanding view that local relapse occurs as a result of tumor cells that persist in the peripheral area of the primary tumor, whereas metastasis is thought to develop from cells that escape into the circulation and remain dormant at distant sites. If tumor cells have the capacity to seed distant sites, the likelihood of the reciprocal situation–tumor cells returning to the site of the primary tumor, even after resection–to repopulate the tumor would seem to be high. Massagué and colleagues now use an assay they termed the "tumor seeding assay," in which a fluorescently labeled "donor" tumor from a human breast, melanoma, or colon cancer cell line is implanted and grown in mice that harbor unlabeled "recipient" tumors at distant sites. Indeed, in most cases donor tumor cells that enter the circulation could be detected in the recipient tumor, where they constituted up to a remarkable 30% of the total cell number. By using trans-endothelial migration assays, the authors identify two cytokines, interleukin-6 (IL-6) and IL-8, that act as paracrine attractants released by the recipient tumors to lure circulating tumor cells back to their site of origin. The reseeding of circulating cells also stimulated tumor vascularization and leukocyte recruitment, enhancing the growth of recipient tumors beyond what was expected from the mere addition of donor cells. The next step is to identify tumor self-seeding in patients, and to devise therapies aimed to create roadblocks for such circulating cancer cells, ultimately curbing their ability go anywhere other than away for good.

M. Y. Kim et al., Tumor self-seeding by circulating cancer cells. Cell 139, 1315–1326 (2009). [Abstract]

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