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

Chen J. et al. 2011. Cancer Cell 19, 541-555

Speaker:  Ming-Hsien Tsai (蔡明憲)                             Time: 13:00~14:00, Apr. 11, 2012

Commentator: Tsai-Wang Chang (張財旺醫師)          Place: Room 601

Abstract:

The infiltration level of tumor-associated macrophages (TAMs) is associated with poor prognosis in patients with breast cancer, but the mechanism remains unclear. TAMs include M1 and M2 phenotypes. M1 macrophages can inhibit tumor growth by exerting cytotoxic effects and secreting inflammatory cytokines, whereas M2 macrophages can promote cancer progression and metastasis by releasing a variety of cytokines. Through the analysis of the cytokine profile of TAMs from breast cancer, the authors found that CCL18 is abundantly expressed. CCL18 is a chemokine predominantly produced by monocyte-derived cells with the M2 phenotype. This chemokine released by breast TAMs promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix (ECM). The authors also identified PITPNM3 as a functional receptor for CCL18 in promoting metastasis and activating intracellular calcium signaling on cancer cells. This chemokine promotes the invasion and metastasis of breast cancer xenografts in the NOD/SCID mouse model, whereas suppressing PITPNM3 abrogates these effects. This study shows that CCL18 is an important TAM-derived cytokine in promoting breast cancer metastasis and suggests that CCL18-PITPNM3 interaction is important for enhancing invasiveness of breast cancer cells.

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