Abstract
C-C chemokine receptor 7 (CCR7) controls lymphocyte migration to secondary lymphoid organs. Although CCR7 has been implicated in targeting the metastasis of cancers to lymph nodes, the role of CCR7 in the metastasis of breast cancer, along with the molecular mechanisms that are controlled by CCR7 that target breast cancer metastasis to the lymph nodes, has yet to be defined. To explore the cellular andmolecular mechanisms of breast cancer cell migration to the lymph nodes, we used the mouse MMTV-PyVmT mammary tumor cells (PyVmT) transfected with CCR7 and the human CCR7-expressing MCF10A and MCF7 mammary cell lines. We found that the CCR7 ligands CCL19 and CCL21, controlled cell migration using the β1-integrin heterodimeric adhesion molecules. To define a physiological significance for CCR7 regulation of migration, we used the FVB syngeneic mouse model of metastatic breast cancer. When CCR7-negative PyVmT cells transfected with control vector were orthotopically transferred to the mammary fat pad of FVB mice, tumors metastasized to the lungs (10/10 mice) but not to the lymph nodes (0/10). In contrast, CCR7-expressing PyVmT (CCR7-PyVmT) cells metastasized to the lymph nodes (6/10 mice) and had a reduced rate of metastasis to the lungs (4/10 mice). CCR7-PyVmT tumors grew significantly faster than PyVmT tumors, which mirrored the growth in vitro, of CCR7-PyVmT, MCF7, and MCF10A mammospheres. This model provides tools for studying lymph node metastasis, CCR7 regulation of tumor cell growth, and targeting of breast cancer cells to the lymph nodes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 354-361 |
| Number of pages | 8 |
| Journal | Translational Oncology |
| Volume | 3 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2010 |
Funding
The authors thank Josiah Cox, Timothy Paul Welch, Nikki Cheng, and Colin Bill for critical comments and for reading the manuscript. The authors thank David Pinson for review of pathology. The authors thank Eric Prossnitz, Donald Morrison, and Nancy Joste for assistance with the human tumor studies. Human flow cytometry data were generated in the Flow Cytometry Facilities, at the University of New Mexico Health Sciences Center, which received support from grants NCRR 1 S10 RR14668, NSF MCB9982161, NCRR P20 RR11830, NCI R24 CA88339, the University of New Mexico Health Sciences Center, and the University of New Mexico Cancer Research and Treatment Center. PyVmT flow cytometry data were generated in the KUMC flow cytometry facilities at the University of Kansas Medical Center, which received support from NIH P20RR016443. The authors thank Shane Stecklein, Tiffany McBurney, and James Deng for technical assistance in development of the mammosphere assay. Address all correspondence to: Charlotte M. Vines, PhD, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd, MSN 3029 66160, Kansas City, KS. E-mail: [email protected] 1C.M.V. received support from National Institutes of Health P20RR016443 and K22AI060815. L.A.S. received support from the KUMC Biomedical Research Training Program. 2H.D.C. and L.A.S. are co-first authors. Received 22 June 2010; Revised 7 September 2010; Accepted 8 September 2010 Copyright © 2010 Neoplasia Press, Inc. All rights reserved 1944-7124/10/$25.00 DOI 10.1593/tlo.10178
ASJC Scopus subject areas
- Oncology
- Cancer Research
