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Homeostatic chemokines guide lymphoma cells to tumor growth-promoting niches within secondary lymphoid organs

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Abstract

The interaction between lymphoid tumor cells and their tissue microenvironment is thought to promote dissemination and progression of lymphoma. Those type of interactions consists of at least three cornerstones, among them mesenchymal- or bone marrow-derived stromal cells, cells of the innate or adaptive immune response, and the lymphoma cells themselves. The molecular pathways of crosstalk between the lymphoma cells and their nursing stroma are not well understood and their dissection is challenging because of (1) the complexity of stroma cell subpopulations, (2) kinetic and developmental transitions/switches of stroma composition, and (3) inherent technical difficulties to isolate and analyze defined stroma cell subsets. However, recent studies of bone marrow stroma interaction with leukemia or lymphoma cells have revealed therapeutic targets involved in regulating tumor cell mobilization. Release of tumor cells from their supportive niches could be effectuated by inhibition of homing and retention signals. The present review focuses on the effects of homing receptors and cytokines attributed to lymphoid tissue formation in tumor–stroma interactions within secondary lymphoid tissues. We discuss possible cellular and molecular mechanisms of lymphoma–stroma crosstalk and highlight novel therapeutic strategies based on the disruption of tumor–stroma interaction in secondary lymphoid organs.

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Acknowledgments

We are grateful to Martin Lipp and Bernd Dörken for helpful discussions and we thank Kristina Schradi for critical reading of the manuscript. This work was supported by the German Cancer Foundation and the Berliner Krebshilfe.

Conflict of interest statement

The authors declare that they have no conflict of interests or financial interests.

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Authors and Affiliations

  1. Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, MDC, Berlin, 13125, Germany

    Uta E. Höpken

  2. Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125, Berlin, Germany

    Armin Rehm

  3. Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, 10117, Germany

    Armin Rehm

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Correspondence to Uta E. Höpken.

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Höpken, U.E., Rehm, A. Homeostatic chemokines guide lymphoma cells to tumor growth-promoting niches within secondary lymphoid organs. J Mol Med 90, 1237–1245 (2012). https://doi.org/10.1007/s00109-012-0906-z

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