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The connectivity of lymphogenous and hematogenous tumor cell dissemination: biological insights and clinical implications

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Abstract

Although tumor cells are found in the blood early after tumorigenesis, dissemination through the lymphatic system and in particular the formation of lymph node metastases has long been considered to be a driving force behind the formation of secondary tumors in distant vital organs. Contemporary experimental observations and clinical trial results suggest that this may not be the case. In this review we survey the evidence for both points of view, and examine the hypothesis that the prognostic relevance of lymph node metastases may lie in their ability to indicate that primary tumors are producing soluble factors that have the potential to promote metastasis at these distant sites, for example by releasing tumor cells from dormancy. Furthermore, the interconnectivity between the lymphatic and blood circulatory systems underscores the relevance of the analysis of the properties of circulating and disseminated tumor cells for prognostic evaluation, patient stratification and understanding the biology of metastasis. We therefore give an overview of the current state of the art in this field.

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Acknowledgments

JPS gratefully acknowledges funding from the European Union under the auspices of the FP7 collaborative project TuMIC, contract no. HEALTH-F2-2008-201662.

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The author declares that there are no conflicts of interest.

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Authors and Affiliations

  1. Centre for Biomedicine and Medical Technology Mannheim (CBTM), Universitätsmedizin Mannheim, University of Heidelberg, TRIDOMUS-Gebäude Haus C, Ludolf-Krehl-Str. 13-17, 68167, Mannheim, Germany

    Jonathan P. Sleeman

  2. KIT Karlsruhe Campus Nord, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Jonathan P. Sleeman

  3. Comprehensive Breast Clinic, Cambridge Hospital, Cambridge, MA, USA

    Blake Cady

  4. Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Klaus Pantel

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  1. Jonathan P. Sleeman
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  2. Blake Cady
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Correspondence to Jonathan P. Sleeman.

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Sleeman, J.P., Cady, B. & Pantel, K. The connectivity of lymphogenous and hematogenous tumor cell dissemination: biological insights and clinical implications. Clin Exp Metastasis 29, 737–746 (2012). https://doi.org/10.1007/s10585-012-9489-x

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