RETRACTED: Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis
Authors: Russell S Taichman
Jianhua Wang
Wenying Song
Cun Yu Wang
Jacques E Nor
Yanxi Sun
Jincheng Wang
Journal: Cellular Signalling (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: metastatic bone lesions; prostate cancer; angiogenesis; stromal-derived factor-1; CXCR4
Affiliations: Department of Periodontics, Prevention and Geriatrics, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109-1078, United States.

Abstract:  The establishment of metastatic bone lesions in prostate cancer (CaP) is a process partially dependent on angiogenesis. Previously we demonstrated that the stromal-derived factor-1 (SDF-1 or CXCL12)/CXCR4 chemokine axis is critical for CaP cell metastasis. In this investigation, cell lines were established in which CXCR4 expression was knocked down using siRNA technology. When CaP cells were co-transplanted with human vascular endothelial cells into SCID mice, significantly fewer human blood vessels were observed paralleling the reductions in CXCR4 levels. Likewise, the invasive behaviors of the CaP cells were inhibited in vitro. From these functional observations we explored angiogenic and signaling mechanisms generated following SDF-1 binding to CXCR4. Differential activation of the MEK/ERK and PI3K/AKT pathways that result in differential secretion IL-6, IL-8, TIMP-2 and VEGF were seen contingent on the cell type examined; VEGF and TIMP-2 expression in PC3 cells are dependent on AKT activation and ERK activation in LNCaP and LNCaP C4-2B cells leads to IL-6 or IL-8 secretion. At the same time, expression of angiostatin levels were inversely related to CXCR4 levels, and inhibited by SDF-1 stimulation. These data link the SDF-1/CXCR4 pathway to changes in angiogenic cytokines by different signaling mechanisms and, suggest that the delicate equilibrium between proangiogenic and antiangiogenic factors may be achieved by different signal transduction pathways to regulate the angiogenic phenotype of prostate cancers. Taken together, our results provide new information regarding expression of functional CXCR4 receptor-an essential role and potential mechanism of angiogenesis upon SDF-1 stimulation. 

Retracted: Yes

PubPeer comments:
 Figure 1B. Could the authors please check? * Blue boxes: The LNCaP C4-2B-control cell panels appear to show an area of overlap with the LNCaP C4-2B-CXCR4-Si cell panels. Of note, zoom, aspect, and exposure factors are all different. ![file] , 
 Figure 6A. * Red boxes: The ERK1 2 panels at 4h and 24h look very similar. ![file] , 
 Figure 6B. * Green boxes and arrows: The top and middle AKT panel look very similar, if one of the two is rotated 180 degrees, stretched differently, and exposed longer. ![file] , 
 In addition to the similarities between the panels of Figure 1B of this 2005 paper, as marked in #1, there also appear to be similarities to panels in Figure 1B of a newer paper by the same research group (same first author). Shown with boxes in two shades of pink. That newer paper is: Jianhua Wang et al., Cancer Research 2007, DOI: 10.1158 0008-5472.can-06-2971 See: https: pubpeer.com publications F812B34F81256487E17917D064C584 Could the authors clarify if these are showing the same experiments? In the 2005 paper the green channel appears to represent CXCR4 expression, while in the 2007 paper it appears to show PGK1 expression. The cells appear different too, but maybe I am misunderstanding what is shown here. ![file] , 
 The b-actin panel in Figure 1A of this older 2005 paper appears to show similarities to the a-Tubulin panels in Figure 1C and 1D of the 2007 paper, although in some occasions mirrored over a horizontal axis. Shown with orange and purple boxes. Note the presence and position of a little dot above one of the lanes. ![file] , 
 Retraction, November 2020. From the retraction notice:  This article has been retracted: please see Elsevier Policy on Article Withdrawal . This article has been retracted at the request of the authors. The corresponding author would like to retract the above paper as Dr. Elisabeth Bik pointed out that some of the figures including Figure 1B, and Figure 6A were duplicated. The corresponding author wishes to convey sincere regret to the editor and readers of the journal of Cellular Signalling. , 
 https: retractionwatch.com 2022 09 26 dental-school-dean-up-to-five-retractions-for-cancer-research-papers , 
 Retraction, November 2020. ,