RETRACTED: Plexin-B1 and Semaphorin 4D Cooperate to Promote Perineural Invasion in a RhoA/ROK-Dependent Manner
Authors: Fabiano O Poswar
Hua Zhou
Ying-Hua Yang
Alfredo M Batista De Paula
Andr√© L Sena Guimar√£es
Yi-Ling Lin
Patrizia Proia
John R Basile
Devaki Sundararajan
Nada O Binmadi
Journal: American Journal Of Pathology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Perineural invasion; PNI; neurotropic malignancies; semaphorins; plexins
Affiliations: Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland; Department of Oral, Basic, and Clinical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland., Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland; Department of Sports Science, University of Palermo, Palermo, Italy., Department of Diagnostic and Surgical Sciences, University of California at Los Angeles, School of Dentistry, Los Angeles, California., Health Science Program, Department of Dentistry, State University of Montes Claros, Minas Gerais, Brazil., Health Science Program, Department of Medicine, State University of Montes Claros, Minas Gerais, Brazil., Department of Oral and Maxillofacial Pathology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts., Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, Baltimore, Maryland; Marlene and Stuart Greenebaum Cancer Center, Baltimore, Maryland. Electronic address: .

Abstract:  Perineural invasion (PNI) is a tropism of tumor cells for nerve bundles located in the surrounding stroma. It is a pathological feature observed in certain tumors, referred to as neurotropic malignancies, that severely limits the ability to establish local control of disease and results in pain, recurrent growth, and distant metastases. Despite the importance of PNI as a prognostic indicator, its biological mechanisms are poorly understood. The semaphorins and their receptors, the plexins, compose a family of proteins originally shown to be important in nerve cell adhesion, axon migration, and proper central nervous system development. Emerging evidence has demonstrated that these factors are expressed in tissues outside of the nervous system and represent a widespread signal transduction system that is involved in the regulation of motility and adhesion in different cell types. We believe that the plexins and semaphorins, which are strongly expressed in both axons and many carcinomas, play a role in PNI. In this study, we show that plexin-B1 is overexpressed in tissues and cell lines from neurotropic malignancies and is attracted to nerves that express its ligand, semaphorin 4D, in a Rho/Rho kinase-dependent manner. We also demonstrate that nerves are attracted to tumors through this same system of proteins, suggesting that both plexin-B1 and semaphorin 4D are important in the promotion of PNI. 

Retracted: Yes

PubPeer comments:
 Fig 1B and 7B have duplicates, could the authors make comments. Thanks! , 
 Dear Dr. Telenomus Theophilae, Thank you very much for pointing out the mistakes in our published manuscript. Both of folders that containing the images in Figure 1B, panel u201c0 dayu201d and Figure 7B, panel u201c0 dayu201d were named as u201c0 dayu201d, which were control group cells without any treatment. During the figure preparation, we used inadvertently the same image for Figure 1B and Figure 7B. But the conclusion of the manuscript was not influenced. We apologize for it and will more carefully process our data in our future work. Thank you again for helping us find and correct the mistake. Hongxin Deng , 
 Could the authors please provide an update on the correction? In addition, Figures 2F and 3D appear to have two images which overlap. While these samples are both controls, it seems that the magnification is different but may be described as the same. Iu2019m unclear on that. ***  ***  ,