| | |  | | | | Record from Web of Science® | | | | | | |
| Involvement of chemokine receptors in breast cancer metastasis |
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| Author(s): Muller A, Homey B, Soto H, Ge NF, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A |
| Source: NATURE Volume: 410 Issue: 6824 Pages: 50-56 Published: MAR 1 2001 |
| Times Cited: 1,590 References: 39 |
| 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-1 alpha 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Zlotnik, A (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, 901 Calif Ave, Palo Alto, CA 94304 USA |
Addresses:
1. DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA
2. Univ Dusseldorf, Dept Radiat Oncol, D-40225 Dusseldorf, Germany
3. Univ Dusseldorf, Dept Dermatol, D-40225 Dusseldorf, Germany
4. Univ Essen, Dept Dermatol, D-45147 Essen, Germany
5. Inst Nacl Cancerol, Mexico City 14000, DF Mexico
6. Natl Autonomous Univ Mexico, Inst Invest Biomed, Mexico City 04510, DF Mexico |
| Publisher: MACMILLAN PUBLISHERS LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 406BD |
| ISSN: 0028-0836 |
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