Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors
2017 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 13, no 1, 476-482 p.Article in journal (Refereed) Published
Prostaglandin E-2 (PGE(2)) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE, receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE(2)-producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including sternness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE(2) signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth.
Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD , 2017. Vol. 13, no 1, 476-482 p.
EP2 receptor; EP2-knockout; prostaglandin E2; cancer; tumor growth; cyclooxygenase
Cancer and Oncology
IdentifiersURN: urn:nbn:se:liu:diva-135403DOI: 10.3892/ol.2016.5448ISI: 000393018400072PubMedID: 28123585OAI: oai:DiVA.org:liu-135403DiVA: diva2:1081486
Funding Agencies|Swedish Cancer Society [CAN 2010/255]; Swedish State under the LUA/ALF agreement; Assar Gabrielsson foundation; Magnus Bergvall foundation2017-03-142017-03-142017-03-14