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      Expression of lipoma preferred partner in mammary and extramammary Paget disease

      research-article
      , RN a , , MM b , , MD, PhD b , , MD, PhD a , , MD, PhD a ,
      Medicine
      Lippincott Williams & Wilkins
      cell motility, immunohistochemistry, lipoma preferred partner, Paget disease

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          Abstract

          Backgound:

          This study aims to identify the expression of lipoma preferred partner (LPP) in Paget disease (PD) and to further understand the pathogenesis of PD.

          Methods:

          Tissue microarray was used to evaluate the expression of LPP by immunohistochemistry in 40 PD patients. The results of LPP expression were combined with clinical and histopathological characteristics. Patient files were analyzed retrospectively.

          Results:

          Twenty-one cases were mammary Paget disease (MPD) and 19 extramammary Paget disease (EMPD) involving the vulva, scrotum, and penis. LPP was expressed in PD and this expression was significantly greater in MPD versus EMPD ( P = .031). The expression of LPP in MPD was significantly related with age ( P = .009) and expression of Ki-67 ( P = .011). No statistically significant differences were observed in LPP expression as related to sex, body location, and time of PD diagnosis.

          Conclusions:

          While LPP is expressed in both MPD and EMPD, the intensity of this expression is greater in MPD. LPP expression is positively correlated with Ki-67 and is more prevalent in middle-aged versus senior MPD patients. Further research is needed to determine its potential role in tumorigenesis and distribution.

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          Most cited references54

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          The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function.

          Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to - and degradation of - the extracellular matrix. The key proteins in these structures include the actin regulators cortactin and neural Wiskott-Aldrich syndrome protein (N-WASP), the adaptor proteins Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and the metalloprotease membrane type 1 matrix metalloprotease (MT1MMP; also known as MMP14). Many cell types can produce these structures, including invasive cancer cells, vascular smooth muscle and endothelial cells, and immune cells such as macrophages and dendritic cells. Recently, progress has been made in our understanding of the regulatory and functional aspects of podosome and invadopodium biology and their role in human disease.
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            Molecular mechanisms of invadopodium formation

            Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma cells. Epidermal growth factor (EGF) receptor kinase inhibitors blocked invadopodium formation in the presence of serum, and EGF stimulation of serum-starved cells induced invadopodium formation. RNA interference and dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation. Time-lapse analysis revealed that invadopodia are formed de novo at the cell periphery and their lifetime varies from minutes to several hours. Invadopodia with short lifetimes are motile, whereas long-lived invadopodia tend to be stationary. Interestingly, suppression of cofilin expression by RNA interference inhibited the formation of long-lived invadopodia, resulting in formation of only short-lived invadopodia with less matrix degradation activity. These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP–Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.
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              Invadopodia are required for cancer cell extravasation and are a therapeutic target for metastasis.

              Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin), maturation (Tks5), or function (Tks4) resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0025-7974
                1536-5964
                18 December 2020
                18 December 2020
                : 99
                : 51
                : e23443
                Affiliations
                [a ]Department of Breast Surgery, The First Affiliated Hospital of China Medical University
                [b ]Department of Dermatology, The First Hospital of China Medical University, Heping District, Shenyang, Liaoning Province, P.R. China.
                Author notes
                []Correspondence: Feng Jin, Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China (e-mail: jinfeng@ 123456cmu.edu.cn ).
                Article
                MD-D-20-04772 23443
                10.1097/MD.0000000000023443
                7748372
                33371071
                2bebf239-4591-4bcc-8e44-25abd8921883
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 25 May 2020
                : 14 September 2020
                : 23 October 2020
                Categories
                5700
                Research Article
                Clinical Trial/Experimental Study
                Custom metadata
                TRUE

                cell motility,immunohistochemistry,lipoma preferred partner,paget disease

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