Cancer and Metastasis Reviews

, Volume 29, Issue 4, pp 695-707

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Perspectives on the mesenchymal origin of metastatic cancer

  • Leanne C. HuysentruytAffiliated withDepartment of Medicine, Hematology and Oncology, University of California, San Francisco
  • , Thomas N. SeyfriedAffiliated withBiology Department, Boston College Email author 


Emerging evidence suggests that many metastatic cancers arise from cells of the myeloid/macrophage lineage regardless of the primary tissue of origin. A myeloid origin of metastatic cancer stands apart from origins involving clonal evolution or epithelial–mesenchymal transitions. Evidence is reviewed demonstrating that numerous human cancers express multiple properties of macrophages including phagocytosis, fusogenicity, and gene/protein expression. It is unlikely that the macrophage properties expressed in metastatic cancers arise from sporadic random mutations in epithelial cells, but rather from damage to an already existing mesenchymal cell, e.g., a myeloid/macrophage-type cell. Such cells would naturally embody the capacity to express the multiple behaviors of metastatic cells. The view of metastasis as a myeloid/macrophage disease will impact future cancer research and anti-metastatic therapies.


Metastatic cancer Myeloid/macrophage lineage Epithelial–mesenchymal transitions Phagocytosis