title: Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors.
abstract: Prostaglandin E2(PGE2) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE2receptor, 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 PGE2-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 stemness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE2signaling 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.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Annika Gustafsson
authors.initials: AG
authors.lastname: Asting
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
authors.affiliation: Department of Geriatric Medicine, Linköping University, SE-581 85 Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Nilsberth
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Smedh
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
keywords: EP2 receptor; EP2-knockout; cancer; cyclooxygenase; prostaglandin E2; tumor growth