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Involvement of chemokine receptors in breast cancer metastasis

Author

Listed:
  • Anja Müller

    (DNAX Research Institute
    Heinrich-Heine University)

  • Bernhard Homey

    (DNAX Research Institute
    Heinrich-Heine University)

  • Hortensia Soto

    (DNAX Research Institute)

  • Nianfeng Ge

    (DNAX Research Institute)

  • Daniel Catron

    (DNAX Research Institute)

  • Matthew E. Buchanan

    (DNAX Research Institute)

  • Terri McClanahan

    (DNAX Research Institute)

  • Erin Murphy

    (DNAX Research Institute)

  • Wei Yuan

    (DNAX Research Institute)

  • Stephan N. Wagner

    (University of Essen)

  • Jose Luis Barrera

    (Instituto Nacional de Cancerología)

  • Alejandro Mohar

    (Instituto Nacional de Cancerología
    Instituto de Investigaciones Biomédicas, Ciudad Universitaria)

  • Emma Verástegui

    (Instituto Nacional de Cancerología)

  • Albert Zlotnik

    (DNAX Research Institute)

Abstract

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Suggested Citation

  • Anja Müller & Bernhard Homey & Hortensia Soto & Nianfeng Ge & Daniel Catron & Matthew E. Buchanan & Terri McClanahan & Erin Murphy & Wei Yuan & Stephan N. Wagner & Jose Luis Barrera & Alejandro Mohar , 2001. "Involvement of chemokine receptors in breast cancer metastasis," Nature, Nature, vol. 410(6824), pages 50-56, March.
    • Handle: RePEc:nat:nature:v:410:y:2001:i:6824:d:10.1038_35065016
    DOI: 10.1038/35065016
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    Cited by:

    1. Minglu Zhou & Chendong Liu & Bo Li & Junlin Li & Ping Zhang & Yuan Huang & Lian Li, 2024. "Cell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Isabel Tundidor & Marta Seijo-Vila & Sandra Blasco-Benito & María Rubert-Hernández & Sandra Adámez & Clara Andradas & Sara Manzano & Isabel Álvarez-López & Cristina Sarasqueta & María Villa-Morales & , 2023. "Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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