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Selectins as Mediators of Lung Metastasis

  • Original Paper
  • Published:
Cancer Microenvironment

Abstract

Lung metastasis remains the major cause of cancer related mortality in patients with breast, gastrointestinal, sarcoma, melanoma and kidney cancer. Here we characterize the expression of selectins during metastatic lung colonization and analyzed their function in the formation of pulmonary metastasis. E-selectin, together with VCAM-1, were detected 6 h after the microvascular arrest of tumor cells indicating an inflammatory activation of the local endothelial cells. No E-selectin expression was detected in pre-metastatic lungs of mice carrying primary tumors. P- and L-selectin were present during initiating steps of lung colonization and correlated with the recruitment of platelets and leukocytes to metastatic tumor cells. Experimental metastasis was significantly reduced in the absence of P- or L-selectin while no attenuation of metastasis was observed in E-selectin-deficient mice. Collectively, selectins are upregulated within the metastatic microenvironment of tumor cells and the formation of a permissive metastatic microenvironment is facilitated by P- and L-selectin mediated interactions between tumor cells and blood components. E-selectin does not affect metastatic initiation in the lung tissue and its expression rather indicates a local activation of lung microvascular endothelial cells.

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Acknowledgements

We thank Eliene O. Kozlowski de Farias for technical assistance. This work was supported by grants from Swiss National Foundation #3100A0-116295 (to L.B.), and from University of Zurich and ZIHP (to H.L.).

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  1. Institute of Physiology, Zürich Center for Integrative Human Physiology, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    Heinz Läubli & Lubor Borsig

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  1. Heinz Läubli
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  2. Lubor Borsig
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Correspondence to Lubor Borsig.

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Supplementary Figure 1

Lung sections of mice subcutaneously injected with 3LL Lewis lung carcinoma cells. Mice were terminated after 24 days and cryosections of lungs were stained with Hematoxilin & Eosin. Representative images of four different mouse specimens are shown. Bar = 100 μm (JPEG 1062 kb)

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Läubli, H., Borsig, L. Selectins as Mediators of Lung Metastasis. Cancer Microenvironment 3, 97–105 (2010). https://doi.org/10.1007/s12307-010-0043-6

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