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RETRACTED ARTICLE: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression

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This article was retracted on 10 March 2020

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Abstract

The semaphorins and plexins comprise a family of cysteine-rich proteins implicated in control of nerve growth and development and regulation of the immune response. Our group and others have found that Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, play an important role in tumor-induced angiogenesis, with some neoplasms producing SEMA4D in a manner analogous to vascular endothelial growth factor (VEGF) in order to attract Plexin-B1-expressing endothelial cells into the tumor for the purpose of promoting growth and vascularity. While anti-VEGF strategies have been the focus of most angiogenesis inhibition research, such treatment can lead to upregulation of pro-angiogenic factors that can compensate for the loss of VEGF, eventually leading to failure of therapy. Here, we demonstrate that SEMA4D cooperates with VEGF to promote angiogenesis in malignancies and can perform the same function in a setting of VEGF blockade. We also show the potential value of inhibiting SEMA4D/Plexin-B1 signaling as a complementary mechanism to anti-VEGF treatment, particularly in VEGF inhibitor–resistant tumors, suggesting that this may represent a novel treatment for some cancers.

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Change history

  • 10 March 2020

    The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled VEGF + VEGFR-2 shRNA has a metadata label of S4d-plexinB1 shRNA2. In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled VEGF shRNA in the published figure, but the metadata label is S4DshRNA-HN121-20X. In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as IgG in the paper, but the metadata show a label of Restore (V+S).tif. The third published image has a label of anti-VEGF IgG, and the metadata show a label of con sh.tif. Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

  • 10 March 2020

    The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figures 1B and 1D, the cell lines are different and all published histograms show SEMA4D mRNA level whereas Excel data have two histograms showing SEMA4D expression and two histograms showing VEGF expression. In Figure 2B, the metadata for one image shows different treatment conditions than those reported in the article. The published image labelled ���VEGF + VEGFR-2 shRNA��� has a metadata label of S4d-plexinB1 shRNA2���. In Figure 2E, statistical significance was shown in the published figure for four comparisons, but upon recalculation, one comparison noted as significant was not. In Figure 6A, the lower left image is labelled ���VEGF shRNA��� in the published figure, but the metadata label is ���S4DshRNA-HN121-20X���. In Figure 6C, specifically, within columns 2-4, for each antibody used for immunocytochemistry, the three images have been swapped so that the original images do not match the shRNA labels in the figure (the labels for the two antibodies were correct). In Figure 7D, the first published image is labelled as ���IgG��� in the paper, but the metadata show a label of ���Restore (V+S).tif���. The third published image has a label of ���anti-VEGF IgG���, and the metadata show a label of ���con sh.tif���. Due to these errors, the Editors-in-Chief have found that the results are no longer reliable.

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Acknowledgments

The authors would like to thank Ernest Smith and Maurice Zauderer of Vaccinex, Inc., for providing the anti-SEMA4D antibody and offering technical support and Daniel Martin and Silvio Gutkind of the National Institute of Dental and Craniofacial Research, NIH, for contributing the head and neck cancer cell lines and assisting in the generation of shRNA lentiviruses. This work was supported by the National Cancer Institute grant R01-CA133162 to J.R.B.

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Authors and Affiliations

  1. Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 West Baltimore Street, 7-North, Baltimore, MD, 21201, USA

    Hua Zhou, Nada O. Binmadi, Ying-Hua Yang, Patrizia Proia & John R. Basile

  2. Department of Oral Basic and Clinical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia

    Nada O. Binmadi

  3. Department of Sports Science (DISMOT), University of Palermo, Via M. Toselli, 87/B, 90143, Palermo, Italy

    Patrizia Proia

  4. Greenebaum Cancer Center, 22 S. Greene Street, Baltimore, MD, 21201, USA

    John R. Basile

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  1. Hua Zhou
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Correspondence to John R. Basile.

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The Editors-in-Chief have retracted this article following an investigation by the University of Maryland. The institution found 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., Binmadi, N.O., Yang, YH. et al. RETRACTED ARTICLE: Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression. Angiogenesis 15, 391–407 (2012). https://doi.org/10.1007/s10456-012-9268-y

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