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Src-signaling interference impairs the dissemination of blood-borne tumor cells

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Abstract

Although solid tumors continuously shed cells, only a small fraction of the neoplastic cells that enter the blood stream are capable of establishing metastases. In order to be successful, these cells must attach, extravasate, proliferate and induce angiogenesis. Preclinical studies have shown that small-molecule ATP-competitive Src kinase inhibitors can effectively impair metastasis-associated tumor cell functions in vitro. However, the impact of these agents on the metastatic cascade in vivo is less well understood. In the present studies, we have examined the ability of saracatinib, a dual-specific, orally available inhibitor of Src and Abl protein tyrosine kinases, to interfere with the establishment of lung metastases in mice by tumor cells introduced into the blood stream. The results demonstrate that Src inhibition most effectively interferes with the establishment of secondary tumor deposits when treatments are administered while tumor cells are in the initial phases of dissemination.

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Acknowledgements

The authors thank Drs. Tim Green and Paul Elvin (AstraZeneca) for scientific discussion.

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Authors and Affiliations

  1. Department of Radiation Oncology and Shands Cancer Center, University of Florida, 2000 SW Archer Road, Gainesville, FL, 32610, USA

    Dietmar W. Siemann, Meiyu Dong & Chris Pampo

  2. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA

    Wenyin Shi

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  1. Dietmar W. Siemann
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  2. Meiyu Dong
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  4. Wenyin Shi
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Correspondence to Dietmar W. Siemann.

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This work was supported in part by a grant from the National Institutes of Health (R01CA089655).

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Siemann, D.W., Dong, M., Pampo, C. et al. Src-signaling interference impairs the dissemination of blood-borne tumor cells. Cell Tissue Res 349, 541–550 (2012). https://doi.org/10.1007/s00441-012-1415-7

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