title: CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3.
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.
authors.affiliation: Breast Tumor Center, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Chen
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yao
authors.forename: Chang
authors.initials: C
authors.lastname: Gong
authors.forename: Fengyan
authors.initials: F
authors.lastname: Yu
authors.forename: Shicheng
authors.initials: S
authors.lastname: Su
authors.forename: Jianing
authors.initials: J
authors.lastname: Chen
authors.forename: Bodu
authors.initials: B
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Fengsong
authors.initials: F
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Herui
authors.initials: H
authors.lastname: Yao
authors.forename: Fengxi
authors.initials: F
authors.lastname: Su
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ewen
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C111792:CCL18 protein, human; D002135:Calcium-Binding Proteins; D019742:Chemokines, CC; D008565:Membrane Proteins; C117885:PITPNM3 protein, human; D012333:RNA, Messenger; D015847:Interleukin-4