Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis (original) (raw)
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- Published: January 2000
Nature Medicine volume 6, pages 100–102 (2000)Cite this article
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Abstract
Metastasis is a frequent complication of cancer, yet the process through which circulating tumor cells form distant colonies is poorly understood. We have been able to observe the steps in early hematogenous metastasis by epifluorescence microscopy of tumor cells expressing green fluorescent protein in subpleural microvessels in intact, perfused mouse and rat lungs. Metastatic tumor cells attached to the endothelia of pulmonary pre-capillary arterioles and capillaries. Extravasation of tumor cells was rare, and it seemed that the transmigrated cells were cleared quickly by the lung, leaving only the endothelium-attached cells as the seeds of secondary tumors. Early colonies were entirely within the blood vessels. Although most models of metastasis include an extravasation step early in the process1, here we show that in the lung, metastasis is initiated by attachment of tumor cells to the vascular endothelium and that hematogenous metastasis originates from the proliferation of attached intravascular tumor cells rather than from extravasated ones. Intravascular metastasis formation would make early colonies especially vulnerable to intravascular drugs, and this possibility has potential for the prevention of tumor cell attachment to the endothelium.
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Acknowledgements
We thank Y. Dong and M. Meuler for technical assistance and W.G. Mckenna and E.J. Bernhard for reading the manuscript. This work was supported by a Parker B. Francis fellowship (A.B.A.), National Institutes of Health RO1 CA46830-09 (R.J.M.) and SCOR P50-HL60290 (A.B.F.), and a Merck Research fellowship (L.S.).
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Authors and Affiliations
- Institute for Environmental Medicine, University of Pennsylvania, 269a John Morgan Building, 3620 Hamilton Walk, Philadelphia, 19104, Pennsylvania, USA
A.B. Al-Mehdi, K. Tozawa & A.B. Fisher - Department of Pathology and Laboratory Medicine, University of Pennsylvania, 269a John Morgan Building, 3620 Hamilton Walk, Philadelphia, 19104, Pennsylvania, USA
L. Shientag, A. Lee & R.J. Muschel
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- A.B. Al-Mehdi
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Correspondence toR.J. Muschel.
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Al-Mehdi, A., Tozawa, K., Fisher, A. et al. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis.Nat Med 6, 100–102 (2000). https://doi.org/10.1038/71429
- Received: 09 September 1999
- Accepted: 08 October 1999
- Issue Date: January 2000
- DOI: https://doi.org/10.1038/71429