Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma of the Lung

Purpose: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protru...

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Veröffentlicht in:Clinical cancer research 2006-04, Vol.12 (8), p.2449-2454
Hauptverfasser: SEMBA, Seitaro, IWAYA, Keiichi, MATSUBAYASHI, Jun, SERIZAWA, Hiromi, KATABA, Hiroaki, HIRANO, Takashi, KATO, Harubumi, MATSUOKA, Takeshi, MUKAI, Kiyoshi
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container_end_page 2454
container_issue 8
container_start_page 2449
container_title Clinical cancer research
container_volume 12
creator SEMBA, Seitaro
IWAYA, Keiichi
MATSUBAYASHI, Jun
SERIZAWA, Hiromi
KATABA, Hiroaki
HIRANO, Takashi
KATO, Harubumi
MATSUOKA, Takeshi
MUKAI, Kiyoshi
description Purpose: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Experimental Design: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Results: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis ( P = 0.0046), and significantly lower in bronchioloalveolar carcinomas ( P < 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time ( P < 0.0001) and overall survival time ( P < 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. Conclusions: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.
doi_str_mv 10.1158/1078-0432.CCR-05-2566
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In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Experimental Design: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Results: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis ( P = 0.0046), and significantly lower in bronchioloalveolar carcinomas ( P &lt; 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time ( P &lt; 0.0001) and overall survival time ( P &lt; 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. Conclusions: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-05-2566</identifier><identifier>PMID: 16638851</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Actin-Related Protein 2 - biosynthesis ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Aged ; Antineoplastic agents ; Arp2/3 complex ; Biological and medical sciences ; Disease-Free Survival ; Female ; Hematologic and hematopoietic diseases ; Humans ; Hymenoptera ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunohistochemistry ; Immunopathology ; lamellipodium ; lung adenocarcinoma ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Medical sciences ; metastasis ; Multivariate Analysis ; Neoplasm Staging ; Pharmacology. 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In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Experimental Design: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Results: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis ( P = 0.0046), and significantly lower in bronchioloalveolar carcinomas ( P &lt; 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time ( P &lt; 0.0001) and overall survival time ( P &lt; 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. 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Immunoglobulinopathies</subject><subject>Immunohistochemistry</subject><subject>Immunopathology</subject><subject>lamellipodium</subject><subject>lung adenocarcinoma</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Multivariate Analysis</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Platelet diseases and coagulopathies</subject><subject>Pneumology</subject><subject>Prognosis</subject><subject>Survival Analysis</subject><subject>Tumors of the respiratory system and mediastinum</subject><subject>WAVE2</subject><subject>Wiskott-Aldrich Syndrome Protein Family - biosynthesis</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuO1DAQRSMEYh7wCSBvQLPx4EfsOMtWxDBILYGG19Jy25WOIbF77LSgP4G_xlE3GnZsyrU4VbfkU1UvKLmmVKg3lDQKk5qz6667w0RgJqR8VJ1TIRrMmRSPS_-XOasucv5OCK0pqZ9WZ1RKrpSg59XvLsKvXYKcfQwo9mhlZx_wHYxmBoc-pjiDD4ghExz65vOPOM94Nbrk7YA-HYJLcQJ0YyY_HtBXSLsURx8A38YpjnEb9_mfHaWsHIRoTbI-xMksgfMAaL0P22fVk96MGZ6f3svqy83bz90tXn94975brbGVVM1YiJYYy4lxkjhgqnFk49q6BSsVF5SYlgnFXe1qSyyrN4L0G8IlJY711NCGX1avj3vLqfd7yLOefLYwjiZAOVfLpi08Z_8FaUNr1XBeQHEEbYo5J-j1LvnJpIOmRC-y9CJCLyJ0kaWJ0IusMvfyFLDfTOAepk52CvDqBJhszdgnE6zPD1xT0ilRhbs6coPfDj99Am0LCalohfLVg6ZMK83quuV_AM1Uq4o</recordid><startdate>20060415</startdate><enddate>20060415</enddate><creator>SEMBA, Seitaro</creator><creator>IWAYA, Keiichi</creator><creator>MATSUBAYASHI, Jun</creator><creator>SERIZAWA, Hiromi</creator><creator>KATABA, Hiroaki</creator><creator>HIRANO, Takashi</creator><creator>KATO, Harubumi</creator><creator>MATSUOKA, Takeshi</creator><creator>MUKAI, Kiyoshi</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20060415</creationdate><title>Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma of the Lung</title><author>SEMBA, Seitaro ; IWAYA, Keiichi ; MATSUBAYASHI, Jun ; SERIZAWA, Hiromi ; KATABA, Hiroaki ; HIRANO, Takashi ; KATO, Harubumi ; MATSUOKA, Takeshi ; MUKAI, Kiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c618t-5590ac30ad60de287d0bd949ec683510a92583d4d4c0c24b50fb03610d2f1a173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Actin-Related Protein 2 - biosynthesis</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Arp2/3 complex</topic><topic>Biological and medical sciences</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Hymenoptera</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunohistochemistry</topic><topic>Immunopathology</topic><topic>lamellipodium</topic><topic>lung adenocarcinoma</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Multivariate Analysis</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Platelet diseases and coagulopathies</topic><topic>Pneumology</topic><topic>Prognosis</topic><topic>Survival Analysis</topic><topic>Tumors of the respiratory system and mediastinum</topic><topic>WAVE2</topic><topic>Wiskott-Aldrich Syndrome Protein Family - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SEMBA, Seitaro</creatorcontrib><creatorcontrib>IWAYA, Keiichi</creatorcontrib><creatorcontrib>MATSUBAYASHI, Jun</creatorcontrib><creatorcontrib>SERIZAWA, Hiromi</creatorcontrib><creatorcontrib>KATABA, Hiroaki</creatorcontrib><creatorcontrib>HIRANO, Takashi</creatorcontrib><creatorcontrib>KATO, Harubumi</creatorcontrib><creatorcontrib>MATSUOKA, Takeshi</creatorcontrib><creatorcontrib>MUKAI, Kiyoshi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SEMBA, Seitaro</au><au>IWAYA, Keiichi</au><au>MATSUBAYASHI, Jun</au><au>SERIZAWA, Hiromi</au><au>KATABA, Hiroaki</au><au>HIRANO, Takashi</au><au>KATO, Harubumi</au><au>MATSUOKA, Takeshi</au><au>MUKAI, Kiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma of the Lung</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2006-04-15</date><risdate>2006</risdate><volume>12</volume><issue>8</issue><spage>2449</spage><epage>2454</epage><pages>2449-2454</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. Experimental Design: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. Results: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis ( P = 0.0046), and significantly lower in bronchioloalveolar carcinomas ( P &lt; 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time ( P &lt; 0.0001) and overall survival time ( P &lt; 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. Conclusions: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16638851</pmid><doi>10.1158/1078-0432.CCR-05-2566</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Actin-Related Protein 2 - biosynthesis
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Aged
Antineoplastic agents
Arp2/3 complex
Biological and medical sciences
Disease-Free Survival
Female
Hematologic and hematopoietic diseases
Humans
Hymenoptera
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunohistochemistry
Immunopathology
lamellipodium
lung adenocarcinoma
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Medical sciences
metastasis
Multivariate Analysis
Neoplasm Staging
Pharmacology. Drug treatments
Platelet diseases and coagulopathies
Pneumology
Prognosis
Survival Analysis
Tumors of the respiratory system and mediastinum
WAVE2
Wiskott-Aldrich Syndrome Protein Family - biosynthesis
title Coexpression of Actin-Related Protein 2 and Wiskott-Aldrich Syndrome Family Verproline-Homologous Protein 2 in Adenocarcinoma of the Lung
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