CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3

Cancer Cell. 2011 Apr 12;19(4):541-55. doi: 10.1016/j.ccr.2011.02.006.


Tumor-associated macrophages (TAMs) can influence cancer progression and metastasis, but the mechanism remains unclear. Here, we show that breast TAMs abundantly produce CCL18, and its expression in blood or cancer stroma is associated with metastasis and reduced patient survival. CCL18 released by breast TAMs promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix. Furthermore, we identify PITPNM3 as a functional receptor for CCL18 that mediates CCL18 effect and activates intracellular calcium signaling. CCL18 promotes the invasion and metastasis of breast cancer xenografts, whereas suppressing PITPNM3 abrogates these effects. These findings indicate that CCL18 derived from TAMs plays a critical role in promoting breast cancer metastasis via its receptor, PITPNM3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / pathology*
  • Calcium-Binding Proteins / physiology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Chemokines, CC / genetics
  • Chemokines, CC / physiology*
  • Female
  • Humans
  • Interleukin-4 / pharmacology
  • Macrophages / physiology*
  • Membrane Proteins / physiology*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Messenger / analysis


  • CCL18 protein, human
  • Calcium-Binding Proteins
  • Chemokines, CC
  • Membrane Proteins
  • PITPNM3 protein, human
  • RNA, Messenger
  • Interleukin-4