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Lysophosphatidic acid (LPA) is a lysophospholipid that acts as a bioactive signaling molecule and plays important roles in diverse biological events during development and disease, including several cancer types. Microglial cells, the resident macrophages of the central nervous system, express high levels of Autotaxin (ATX,Enpp2), an enzyme that synthetizes LPA. Our study aimed to investigate the role of LPA on tumor growth and invasion in the context of microglia\u2010GBM interaction. First, through bioinformatics studies, patient data analysis demonstrated that more aggressive GBM expressed higher levels of ENPP2, which was also associated with worse patient prognosis with proneural GBM. Using GBM\u2010microglia co\u2010culture system we then demonstrated that GBM secreted factors were able to increase LPA\n                      <jats:sub>1<\/jats:sub>\n                      and ATX in microglia, which could be further enhanced by hypoxia. On the other hand, interaction with microglial cells also increased ATX expression in GBM. Furthermore, microglial\u2010induced GBM proliferation and migration could be inhibited by pharmacological inhibition of LPA\n                      <jats:sub>1<\/jats:sub>\n                      , suggesting that microglial\u2010derived LPA could support tumor growth and invasion. Finally, increased LPA\n                      <jats:sub>1<\/jats:sub>\n                      expression was observed in GBM comparing with other gliomas and could be also associated with worse patient survival. These results show for the first time a microglia\u2010GBM interaction through the LPA pathway with relevant implications for tumor progression. A better understanding of this interaction can lead to the development of new therapeutic strategies setting LPA as a potential target for GBM treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15097-fig-0008-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.15097","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T18:52:45Z","timestamp":1590087165000},"page":"499-512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Microglial lysophosphatidic acid promotes glioblastoma proliferation and migration via LPA\n                    <sub>1<\/sub>\n                    receptor"],"prefix":"10.1111","volume":"156","author":[{"given":"Rackele F.","family":"Amaral","sequence":"first","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz H. 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