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

By Jingqi Chen, Yandan Yao, C. Gong, F. Yu, Shicheng Su, Jianing Chen, Bodu Liu, Hui Deng, Fengsong Wang, Ling Lin and 7 more. Cancer Cell, 2011

601 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/aa2967e322d64cac00285eb74a341677de0b690b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. C. Roma-Rodrigues
2. Alexandra R. Fernandes
3. R. Mendes
4. Pedro Viana Baptista

In Oncology

1. C. Roma-Rodrigues
2. Alexandra R. Fernandes
3. R. Mendes
4. Pedro Viana Baptista

Citations in the corpus

• Macrophage plasticity and polarization: in vivo veritas. (2012, unknown): “TAM infiltration is generally associated with poor prognosis, as shown in Hodgkin disease, glioma, cholangiocarcinoma, and breast carcinoma (87, 88).”
• Stroma Cells in Tumor Microenvironment and Breast Cancer (2012, unknown): “Importantly, the results indicated that the functional receptor of CCL18, PITPNM3, is able to promote breast cancer progression through the interaction of CCL18 and PITPNM3.”
• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, unknown): “PITPNM3 has now been implicated in breast cancer metastasis, acting in response to CCL18 release from tumor-associated macrophages (Chen et al., 2011).”
• Targeting Tumor Microenvironment for Cancer Therapy (2019, background): “A high number of TAMs at the TME is generally accompanied by a poor prognosis [12,74,78].”
• Tumor-associated macrophages: from basic research to clinical application (2017, background): “In human xenograft models, CCL18 is also required for tumor cell invasion and metastasis, playing a role in integrin clustering [41].”
• Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells (2016, background): “, 2013), is highly expressed in different tumors including NSCLC (Chen et al., 2011; Schutyser et al., 2005).”