Editors' ChoiceMEDICINE

Rethinking Cancer Metastasis

Science Signaling  30 Sep 2008:
Vol. 1, Issue 39, pp. ec341
DOI: 10.1126/scisignal.139ec341

Most human cancer deaths are caused by metastasis, in which cancer cells spread from the primary tumor to new sites in the body. Because metastatic cells must successfully negotiate a series of complex steps, including survival in the bloodstream and establishment in a foreign tissue environment, metastasis has been viewed as a late event in cancer progression. Podsypanina et al. (see the Perspective by Klein) suggest that the metastatic process may begin earlier than previously thought. Normal mouse mammary cells were genetically manipulated to allow the timing of oncogene expression to be experimentally controlled and injected into the bloodstream of mice. Surprisingly, in the absence of oncogene expression, normal mammary cells were capable of traveling to and surviving in the lungs for up to 16 weeks, although they did not initiate aggressive growth until after oncogene activation. Thus, metastases might arise from disseminated normal (premalignant) cells that remain clinically silent until genetic changes render them malignant.

K. Podsypanina, Y.-C. N. Du, M. Jechlinger, L. J. Beverly, D. Hambardzumyan, H. Varmus, Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321, 1841-1844 (2008). [Abstract] [Full Text]

C. A. Klein, The metastasis cascade. Science 321, 1785-1787 (2008). [Summary] [Full Text]

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