Role of CXCL12-CXCR4 axis in ovarian cancer metastasis and CXCL12-CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro
Authors: Yan Liu
Yan-Nan Chen
Yi-Ming Xu
Chen-Chen Ren
Li Yang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMD3100; CXCL12-CXCR4 axis; apoptosis; invasion; migration
Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract:  Ovarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to the head. CXCL12 and its receptor chemokine receptor 4 ( CXCR4) have been found to be highly expressed in OC and contribute to the disease progression by affecting tumor cell proliferation and invasion. Here, in this study, we aim to explore whether the blockade of CXCL12-CXCR4 axis with AMD3100 (a selective CXCR4 antagonist) has effects on the progression of OC. On the basis of the gene expression omnibus database of OC gene expression chips, the OC differentially expressed genes were screened by microarray analysis. OC (nonmetastatic and metastatic) and normal ovarian tissues were collected to determine the expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and pCNS-CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was assessed. Cell viability, apoptosis, migration, and invasion were all evaluated. The microarray analysis screened out the differential expression of CXCL12-CXCR4 in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was observed to have a critical role in inhibiting cell proliferation, migration, and invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed CXCR4 brought significantly promoting effects on the proliferation and invasiveness of OC cells. These results reinforce that the blockade of CXCL12-CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of the inhibition of CXCL12-CXCR4 axis offers a preclinical validation of CXCL12-CXCR4 axis as a therapeutic target in OC. 

Retracted: Yes

PubPeer comments:
 In this paper, ovarian cancer tissues from 33 women with metastatic OC and 36 women with non-metastatic OC were examined. Figure 2: * Blue boxes: The non-metastatic tumor panel appears to show an overlap with the metastatic tumor panel. ![file] , 
 * Figure 6B: Some Western blots in this figure appear to look very similar to the  Sewing-machine bands as described in a recent post by Smut Clyde on Leonid Schneider s blog: https: forbetterscience.com 2020 09 14 dead-horses-wont-flog-themselves ![file] , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 07 September 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. As several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. ,