Abstract
Semaphorin 4D (SEMA4D) is a member of a family of transmembrane and secreted proteins that have been shown to act through its receptor Plexin-B1 to regulate axon growth cone guidance, lymphocyte activation, and bone density. SEMA4D is also overexpressed by some malignancies and plays a role in tumor-induced angiogenesis similar to vascular endothelial growth factor (VEGF), a protein that has been targeted as part of some cancer therapies. In an attempt to examine the different effects on tumor growth and vascularity for these two pro-angiogenic factors, we previously noted that while inhibition of both VEGF and SEMA4D restricted tumor vascularity and size, vessels forming under conditions of VEGF blockade retained their association with pericytes while those arising in a background of SEMA4D/Plexin-B1 deficiency did not, an intriguing finding considering that alteration in pericyte association with endothelial cells is an emerging aspect of anti-angiogenic intervention in the treatment of cancer. Here we show through array analysis, immunoblots, migration and co-culture assays and VE-cadherin immunohistochemistry that SEMA4D production by head and neck carcinoma tumor cells induces expression of platelet-derived growth factor-B and angiopoietin-like protein 4 from endothelial cells in a Plexin-B1/Rho-dependent manner, thereby influencing proliferation and differentiation of pericytes and vascular permeability, whereas VEGF lacks these effects. These results partly explain the differences observed between SEMA4D and VEGF in pathological angiogenesis and suggest that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of solid tumors.
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26 February 2020
The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figure 1C, the graph showing PDGF-B does not match the original data for the 24-hour time point. The graph shows the value to be over 1000 pg/ml, but the original data have a value of 106.626. In Figure 1F, the data were entered manually to create the standard deviation bars. The data manually entered do not match the original data. When the standard deviations for the original data were calculated, the p values were no longer significant using a paired student t test. In Figure 2C, the original data do not match the published data. In Figure 4B, the images in the first lane and the fifth lane are from the same micrograph (i.e., the same set of conditions). However, the published figure claims that they are different conditions. The metadata in this figure also shows different cell lines than those noted in the article. The first and last images are labelled as Du145 shAR3 anti AR3.jpg. The second image is labelled as Du145 shAR8 anti AR8.jpg. The third image is labelled as Cos1 mARs3 mS3-2 antibody-2.jpg. The fourth image is labelled as R1 3634 bleed.jpg. Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.
26 February 2020
The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figure 1C, the graph showing PDGF-B does not match the original data for the 24-hour time point. The graph shows the value to be over 1000 pg/ml, but the original data have a value of 106.626. In Figure 1F, the data were entered manually to create the standard deviation bars. The data manually entered do not match the original data. When the standard deviations for the original data were calculated, the p values were no longer significant using a paired student t test. In Figure 2C, the original data do not match the published data. In Figure 4B, the images in the first lane and the fifth lane are from the same micrograph (i.e., the same set of conditions). However, the published figure claims that they are different conditions. The metadata in this figure also shows different cell lines than those noted in the article. The first and last images are labelled as ���Du145 shAR3 anti AR3.jpg���. The second image is labelled as ���Du145 shAR8 anti AR8.jpg���. The third image is labelled as ���Cos1 mARs3 mS3-2 antibody-2.jpg.��� The fourth image is labelled as ���R1 3634 bleed.jpg���. Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.
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Acknowledgments
We would like to acknowledge Dr. Snigdha Banerjee for the use of C3H/10T1/2 embryonic mesenchymal stem cells. This work was supported by the National Cancer Institute grant R01-CA133162 to J.R.B.
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The authors declare that they have no conflict of interest.
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The Editors-in-Chief have retracted this article following an investigation by the University of Maryland. The institution found that problems in some figures. Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.
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Zhou, H., Yang, YH. & Basile, J.R. RETRACTED ARTICLE: The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4. Angiogenesis 17, 261–274 (2014). https://doi.org/10.1007/s10456-013-9395-0
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DOI: https://doi.org/10.1007/s10456-013-9395-0