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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 \u03b2 (TGF\u03b2) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization <jats:italic>in vivo<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/srep10071","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T12:59:56Z","timestamp":1431349196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling"],"prefix":"10.1038","volume":"5","author":[{"given":"Xu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,5,11]]},"reference":[{"key":"BFsrep10071_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S1055-3207(03)00130-3","volume":"13","author":"P Mojica-Manosa","year":"2004","unstructured":"Mojica-Manosa, P., Reidy, J., Wilson, K. & Douglas, W. 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