title: Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling.
abstract: Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, PLGF secreted by LC cells triggered macrophage polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be activated in the PLGF-polarized TAM via transforming growth factor β (TGFβ) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization in vivo, and significantly promoted the growth of LC. Thus, together with our previous work, our study highlights a pivotal role of cross-talk between TAM and LC in regulating the metastasis of LC.
authors.affiliation: 1] Otorhinolaryngology Department, Zhongshan Hospital, Fu Dan University, 180 Fenglin Road, Shanghai 200032, China [2] State Key Laboratory of Molecular Engineering of Polymers (Fudan University), 220 Handan Road, Shanghai 200433, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Otorhinolaryngology Department, Zhongshan Hospital, Fu Dan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D016212:Transforming Growth Factor beta; D000072483:Placenta Growth Factor; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse