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Prostate cancer expressing membrane-bound TGF-α induces bone formation mediated by the autocrine effect of prostaglandin E 2 in osteoblasts.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Feb 12; Vol. 644, pp. 40-48. Date of Electronic Publication: 2022 Nov 24. - Publication Year :
- 2023
-
Abstract
- Prostate cancer highly metastasizes to bone, and such cancer is associated with severe bone resorption and bone formation at the site of metastasis. Prostaglandin E <subscript>2</subscript> (PGE <subscript>2</subscript> ) promotes bone resorption in inflammatory diseases; however, the roles in prostate cancer-induced bone formation are still unclear. In the present study, we investigated the effects of membrane-bound TGF-α on prostate cancer-induced bone formation through autocrine PGE <subscript>2</subscript> signaling in osteoblasts. In the prostate cancer explant experiment into tibiae, injected prostate cancer cells induced bone formation with the increased expression of osteogenic genes, such as Runx2 and Wnt5a, and prostaglandin synthase Ptgs2. In osteoblasts, PGE <subscript>2</subscript> increased the number of calcified bone nodules with enhanced expression of Runx2 and Wnt5a. We also screened the factors involved in cancer progression, and 11 EGF family members were found to be expressed in the human prostate cancer cell line PC3. PC3 highly expressed amphiregulin, HB-EGF, and especially TGF-α. Treatment with recombinant TGF-α increased the Ptgs2 expression and PGE <subscript>2</subscript> production in osteoblasts, which promoted the formation of calcified bone nodules, suggesting that the interaction between PC3 and osteoblasts promoted PGE <subscript>2</subscript> production. In co-culture of osteoblasts and fixed PC3 cells, the phosphorylation of EGFR and ERK and subsequent Ptgs2 expression and PGE <subscript>2</subscript> production were increased, an effect that was attenuated by treatment with inhibitors of EGFR and ERK. These results indicate that membrane-bound TGF-α enhances ERK signaling while also inducing PGE <subscript>2</subscript> -mediated bone formation in osteoblasts, thus suggesting that prostate cancer regulates both PGE <subscript>2</subscript> -mediated bone resorption and bone formation at the site of bone metastasis of prostate cancer.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Male
Core Binding Factor Alpha 1 Subunit metabolism
Cyclooxygenase 2 metabolism
ErbB Receptors metabolism
Osteoblasts metabolism
Osteogenesis
Prostaglandins metabolism
Transforming Growth Factor alpha metabolism
Dinoprostone metabolism
Bone Resorption metabolism
Prostatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 644
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 36623397
- Full Text :
- https://doi.org/10.1016/j.bbrc.2022.11.050