CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3

Jingqi Chen, Yandan Yao, Chang Gong, Fengyan Yu, Shicheng Su, Jianing Chen, Bodu Liu, Hui Deng, Fengsong Wang, Ling Lin, Herui Yao, Fengxi Su, Karen S. Anderson, Qiang Liu, Mark E. Ewen, Xuebiao Yao, Erwei Song

Research output: Contribution to journalArticlepeer-review

508 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)541-555
Number of pages15
JournalCancer cell
Volume19
Issue number4
DOIs
StatePublished - Apr 12 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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