Involvement of chemokine receptors in breast cancer metastasis

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, Emma Verástegui and Albert Zlotnik ()
Additional contact information
Anja Müller: DNAX Research Institute
Bernhard Homey: DNAX Research Institute
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
Emma Verástegui: Instituto Nacional de Cancerología
Albert Zlotnik: DNAX Research Institute

Nature, 2001, vol. 410, issue 6824, 50-56

Abstract: 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.

Date: 2001
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DOI: 10.1038/35065016

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