PMID- 21855541 OWN - NLM STAT- MEDLINE DCOM- 20111219 LR - 20110913 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 317 IP - 17 DP - 2011 Oct 15 TI - N-cadherin mediates angiogenesis by regulating monocyte chemoattractant protein-1 expression via PI3K/Akt signaling in prostate cancer cells. PG - 2512-21 LID - 10.1016/j.yexcr.2011.07.024 [doi] AB - Over the past decade, evidence continues to mount showing that N-cadherin is a critical protein in cancer progression and metastasis. In the present study, we evaluated the expression of N-cadherin in human prostate cancer tissue specimens and cell lines. Enhanced expression of N-cadherin was observed in both the malignant and bone-metastasized prostate tissue specimens compared to the healthy prostate tissues. Consistent with the tissue array data, N-cadherin was highly expressed in PC3, but not in Du145 and LNCaP human prostate cell lines. Based on cell to cell binding assay, we found that N-cadherin expression facilitates homotypic interaction between human prostate cancer cells and human microvascular endothelial cells (HMEC). Human angiogenesis antibody array and in vitro angiogenesis assay showed that siRNA-mediated knockdown of N-cadherin reduced the secretion of monocyte chemoattractant protein-1 (MCP-1), which played a potential role in stimulating capillary network formation of HMEC. Additionally, culture supernatant of Du145 cells transfected with full-length N-cadherin expressing plasmid showed increased MCP-1 expression and chemoattractant ability compared to normal Du145 cells. Further, we noticed that blocking PI3K activity inhibited N-cadherin mediated MCP-1 expression. Our data demonstrated that N-cadherin in prostate cancer cell mediates cell-cell adhesion and regulates MCP-1 expression via the PI3K/Akt signaling pathway. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Nalla, Arun Kumar AU - Nalla AK AD - Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA. FAU - Estes, Norman AU - Estes N FAU - Patel, Jitendra AU - Patel J FAU - Rao, Jasti S AU - Rao JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110809 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Antigens, CD) RN - 0 (CDH2 protein, human) RN - 0 (Cadherins) RN - 0 (Chemokine CCL2) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Antigens, CD/biosynthesis/genetics/*metabolism MH - Cadherins/biosynthesis/genetics/*metabolism MH - Cell Adhesion MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/metabolism MH - Humans MH - Male MH - Neovascularization, Pathologic/*metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Prostatic Neoplasms/*metabolism/pathology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - *Signal Transduction EDAT- 2011/08/23 06:00 MHDA- 2011/12/20 06:00 CRDT- 2011/08/23 06:00 PHST- 2011/05/25 00:00 [received] PHST- 2011/07/27 00:00 [revised] PHST- 2011/07/29 00:00 [accepted] PHST- 2011/08/23 06:00 [entrez] PHST- 2011/08/23 06:00 [pubmed] PHST- 2011/12/20 06:00 [medline] AID - S0014-4827(11)00310-7 [pii] AID - 10.1016/j.yexcr.2011.07.024 [doi] PST - ppublish SO - Exp Cell Res. 2011 Oct 15;317(17):2512-21. doi: 10.1016/j.yexcr.2011.07.024. Epub 2011 Aug 9.