CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages

Pulmonary metastasis of breast cancer cells is promoted by a distinct population of macrophages, metastasis-associated macrophages (MAMs), which originate from inflammatory monocytes (IMs) recruited by the CC-chemokine ligand 2 (CCL2). We demonstrate here that, through activation of the CCL2 receptor CCR2, the recruited MAMs secrete another chemokine ligand CCL3. Genetic deletion of CCL3 or its receptor CCR1 in macrophages reduces the number of lung metastasis foci, as well as the number of MAMs accumulated in tumor-challenged lung in mice. Adoptive transfer of WT IMs increases the reduced number of lung metastasis foci in Ccl3 deficient mice. Mechanistically, Ccr1 deficiency prevents MAM retention in the lung…

• UD
  U.S. Department of Defense

  Award: DOD#W81xWH-11-1-0703
• WT
  Wellcome Trust

  Awards: 101067, 101067/Z/13/Z
• NI
  National Institutes of Health

  Awards: PO1 CA100324, MDA-MB-231, CA172451, CA100324
• CD
  Congressionally Directed Medical Research Programs

  Award: DOD#W81xWH-11-1-0703