The Role of Fascin in the Migration and Invasiveness = of Malignant Glioma Cells

From: Subject: The Role of Fascin in the Migration and Invasiveness of Malignant Glioma Cells Date: Fri, 29 Feb 2008 11:50:30 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0037_01C87AC9.48D14AB0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.3198 This is a multi-part message in MIME format. ------=_NextPart_000_0037_01C87AC9.48D14AB0 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2244690&rendertype=abstract =EF=BB=BF The Role of Fascin in the Migration and Invasiveness = of Malignant Glioma Cells

Journal=20 List > Neoplasia=20 > v.1= 0(2);=20 Feb 2008

PubMed=20 articles by:

Hyun Hwang, J.

Smith, C.

Salhia, B.

Rutka, = J.

Neoplasia. = 2008 February; = 10(2):=20 149=E2=80=93159.

PMCID:=20 PMC2244690

The Role of Fascin in the Migration and = Invasiveness=20 of Malignant Glioma Cells¹

Jeong Hyun=20 Hwang,^*^=E2=80=A0 Christian A = Smith,^=E2=80=A0 Bodour=20 Salhia,^=E2=80=A1 and James T Rutka^=E2=80=A0

^*Department of Neurosurgery, = School of=20 Medicine, Kyungpook National University, Daegu, South Korea

^=E2=80=A0The Arthur and Sonia = Labatt Brain Tumor=20 Research Center, The Hospital for Sick Children, The University of = Toronto, Toronto, Ontario, Canada

^=E2=80=A1The Translational = Genomics Research=20 Institute, Phoenix, AZ, USA

Address all correspondence to: James T. = Rutka, MD,=20 PhD, Division of Neurosurgery, Suite 1503, The Hospital for Sick = Children,=20 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. E-mail: = james.rutka/at/sickkids.ca

Received October 11, 2007; Revised = November 28,=20 2007; Accepted November 28, 2007.

Abstract

Malignant glioma is the most common = primary=20 brain tumor, and its ability to invade the surrounding brain = parenchyma is=20 a leading cause of tumor recurrence and treatment failure. Whereas = the=20 molecular mechanisms of glioma invasion are incompletely = understood, there=20 is growing evidence that cytoskeletal-matrix interactions = contribute to=20 this process. Fascin, an actin-bundling protein, induces parallel = actin=20 bundles in cell protrusions and increases cell motility in = multiple human=20 malignancies. The role of fascin in glioma invasion remains = unclear. We=20 demonstrate that fascin is expressed in a panel of human malignant = glioma=20 cell lines, and downregulation of fascin expression in glioma cell = lines=20 by small interfering RNA (siRNA) is associated with decreased = cellular=20 attachment to extracellular matrix (ECM) and reduced migration. = Using=20 immunofluorescence analysis, we show that fascin depletion results = in a=20 reduced number of filopodia as well as altered glioma cell shape. = In=20 vitro invasiveness of U251, U87, and SNB19 glioma cells was = inhibited=20 by fascin siRNA treatment by 52.2%, 40.3%, and 23.8% respectively. = Finally, we show a decreased invasiveness of U251-GFP cells by = fascin=20 knockdown in an ex vivo rat brain slice model system. This is the = first=20 study to demonstrate a role for fascin in glioma cell morphology,=20 motility, and invasiveness.

Articles=20 from Neoplasia (New = York,=20 N.Y.) are provided here courtesy of
Neoplasia=20 Press

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DIV.panel { BORDER-RIGHT: gray 1px solid; PADDING-RIGHT: 0px; BORDER-TOP: gray 1px = solid; PADDING-LEFT: 0px; FLOAT: left; PADDING-BOTTOM: 0px; MARGIN: 0px; = BORDER-LEFT: gray 1px solid; PADDING-TOP: 0px; BORDER-BOTTOM: gray 1px = solid; BACKGROUND-COLOR: #ecf0f4 } DIV.panel P { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; MIN-HEIGHT: 21px; FLOAT: left; = PADDING-BOTTOM: 0.2em; MARGIN: 0px; WIDTH: 100%; PADDING-TOP: 0.1em; = BACKGROUND-COLOR: #ecf0f4; TEXT-ALIGN: center } DIV.panel P SPAN { PADDING-LEFT: 25px; FLOAT: left; MARGIN: 0px; WIDTH: 85% } DIV.panel P A { DISPLAY: none; MIN-HEIGHT: 21px; TEXT-DECORATION: none } DIV.panel P A.active { BACKGROUND-POSITION: 13px 0px; DISPLAY: block; FLOAT: right; = BACKGROUND-IMAGE: url(i/toolbar.png); MARGIN: 0px 9px 0px 0px; WIDTH: = 36px; BACKGROUND-REPEAT: no-repeat; HEIGHT: 21px; _background-image: = url(i/toolbar.gif); _margin-right: 5px } DIV.panel P A.active:hover { BACKGROUND-POSITION: -67px 0px; BACKGROUND-REPEAT: no-repeat; = BACKGROUND-COLOR: #ecf0f4; TEXT-DECORATION: none } DIV.panel DL { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: = 0px; PADDING-TOP: 0px } DIV.panel DD { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: = 0px; PADDING-TOP: 0px } DIV.panel DT { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: = 0px; PADDING-TOP: 0px } DIV.panel DT IMG { PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: = 0px; PADDING-TOP: 0px } DIV.panel DL { FLOAT: left; WIDTH: 100% } DIV.panel DL DD { FLOAT: right } DIV.panel DL DT { FLOAT: left; BACKGROUND-IMAGE: url(i/loading_bg.gif) } .scale-pmc { MARGIN: auto; WIDTH: 32px; PADDING-TOP: 0em } .scale-pmc A { PADDING-RIGHT: 1px; DISPLAY: block; PADDING-LEFT: 1px; FONT-SIZE: 3px; = BACKGROUND-IMAGE: url(i/toolbar.png); PADDING-BOTTOM: 1px; MARGIN: 0px; = PADDING-TOP: 1px; BACKGROUND-REPEAT: no-repeat; HEIGHT: 16px; = TEXT-DECORATION: none; _background-image: url(i/toolbar.gif) } .scale-pmc A:hover { BACKGROUND-REPEAT: no-repeat; BACKGROUND-COLOR: transparent; = TEXT-DECORATION: none } .scale-pmc A.scale-up { MARGIN: 2px auto; WIDTH: 22px; HEIGHT: 22px } .scale-pmc A.scale-up-disabled { MARGIN: 2px auto; WIDTH: 22px; HEIGHT: 22px } .scale-pmc A.scale-down-disabled { MARGIN: 2px auto; WIDTH: 22px; HEIGHT: 22px } .scale-pmc A.scale-down { MARGIN: 2px auto; WIDTH: 22px; HEIGHT: 22px } .scale-pmc A.scale-up { BACKGROUND-POSITION: 4px -26px } .scale-pmc A.scale-up:hover { BACKGROUND-POSITION: -76px -26px } .scale-pmc A.scale-up-disabled { BACKGROUND-POSITION: -36px -26px; CURSOR: default } .scale-pmc A.scale-down { BACKGROUND-POSITION: 4px -226px } .scale-pmc A.scale-down:hover { BACKGROUND-POSITION: -76px -226px } .scale-pmc A.scale-down-disabled { BACKGROUND-POSITION: -36px -226px; CURSOR: default } .scale-pmc A.scale-1 { BACKGROUND-POSITION: 3px -57px } .scale-pmc A.scale-1:hover { BACKGROUND-POSITION: -77px -57px } .scale-pmc A.selected-1 { BACKGROUND-POSITION: -37px -57px; CURSOR: default } .scale-pmc A.selected-1:hover { BACKGROUND-POSITION: -37px -57px; CURSOR: default } .scale-pmc A.scale-2 { BACKGROUND-POSITION: 3px -77px } .scale-pmc A.scale-2:hover { BACKGROUND-POSITION: -77px -77px } .scale-pmc A.selected-2 { BACKGROUND-POSITION: -37px -77px; CURSOR: default } .scale-pmc A.selected-2:hover { BACKGROUND-POSITION: -37px -77px; CURSOR: default } .scale-pmc A.scale-3 { BACKGROUND-POSITION: 3px -97px } .scale-pmc A.scale-3:hover { BACKGROUND-POSITION: -77px -97px } .scale-pmc A.selected-3 { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.selected-3:hover { BACKGROUND-POSITION: -37px -97px; CURSOR: default } .scale-pmc A.scale-4 { BACKGROUND-POSITION: 3px -117px } .scale-pmc A.scale-4:hover { BACKGROUND-POSITION: -77px -117px } .scale-pmc A.selected-4 { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.selected-4:hover { BACKGROUND-POSITION: -37px -117px; CURSOR: default } .scale-pmc A.scale-5 { BACKGROUND-POSITION: 3px -137px } .scale-pmc A.scale-5:hover { BACKGROUND-POSITION: -77px -137px } .scale-pmc A.selected-5 { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.selected-5:hover { BACKGROUND-POSITION: -37px -137px; CURSOR: default } .scale-pmc A.scale-6 { BACKGROUND-POSITION: 3px -157px } .scale-pmc A.scale-6:hover { BACKGROUND-POSITION: -77px -157px } .scale-pmc A.selected-6 { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.selected-6:hover { BACKGROUND-POSITION: -37px -157px; CURSOR: default } .scale-pmc A.scale-7 { BACKGROUND-POSITION: 3px -177px } .scale-pmc A.scale-7:hover { BACKGROUND-POSITION: -77px -177px } .scale-pmc A.selected-7 { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.selected-7:hover { BACKGROUND-POSITION: -37px -177px; CURSOR: default } .scale-pmc A.scale-8 { BACKGROUND-POSITION: 3px -207px } .scale-pmc A.scale-8:hover { BACKGROUND-POSITION: -77px -207px } .scale-pmc A.selected-8 { BACKGROUND-POSITION: -37px -207px; CURSOR: default } .scale-pmc A.selected-8:hover { BACKGROUND-POSITION: -37px -207px; CURSOR: default } ------=_NextPart_000_0037_01C87AC9.48D14AB0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.pubmedcentral.nih.gov/corehtml/pmc/js/common.js // Called from many places to handle links.=0A= // Params:=0A= // link: URL. 'this' to reuse same window, else ""=0A= // windowname: Reference name for window=0A= // additional: Attributes for window.open, from:=0A= // width, height, resizable, scrollbars, toolbar, location, = directories,=0A= // status, menubar, copyhistory.=0A= // Notes: Book version always provides menubar, toolbar, etc.=0A= //=0A= function startTargetBook(link,windowname,width,height,additional) =0A= {=0A= if(! window.focus)=0A= return;=0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= var opt =3D = "menubar=3Dyes,toolbar=3Dyes,status=3Dyes,scrollbars,resizable,dependent=3D= yes";=0A= var allOptions =3D opt + sizestring;=0A= if (additional) { allOptions =3D allOptions + additional; }=0A= //alert("In startTargetBook, additional: " + additional);=0A= =0A= w =3D window.open("",windowname, allOptions);=0A= w.focus();=0A= link.target=3Dwindowname;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function startTarget(link,windowname,width,height) =0A= {=0A= if(! window.focus)=0A= return;=0A= var sizestring =3D ",width=3D" + width + ",height=3D" + height;=0A= w =3D = window.open("",windowname,"scrollbars,resizable,dependent=3Dyes" + = sizestring);=0A= w.focus();=0A= link.target=3Dwindowname;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function focuswin(windowname) =0A= {=0A= w =3D = window.open("",windowname,"menubar=3Dyes,scrollbars=3Dyes,toolbar=3Dyes,l= ocation=3Dyes,status=3Dyes,directories=3Dyes,resizable=3Dyes");=0A= w.focus();=0A= return true;=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseString (inStr)=0A= {=0A= var outStr =3D ''=0A= =0A= for (i =3D0; i <=3D inStr.length; i++)=0A= {=0A= outStr =3D inStr.charAt(i) + outStr=0A= }=0A= =0A= return outStr=0A= }=0A= =0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function reverseAndReplaceString (inStr, findStr, newStr)=0A= {=0A= return reverseString(inStr).replace(findStr, newStr)=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function initUnObscureEmail (className, innerHTML)=0A= {=0A= =0A= try{=0A= if (window.addEventListener)=0A= window.addEventListener('load', function() {unObscureEmail = (className, innerHTML)}, false)=0A= else if (window.attachEvent)=0A= window.attachEvent('onload', function() {unObscureEmail = (className, innerHTML)})=0A= }catch(e){=0A= }=0A= }=0A= =0A= //=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=0A= function unObscureEmail (className, innerHTML)=0A= {=0A= try {=0A= if (typeof(unObscuredEmails) =3D=3D 'undefined')=0A= unObscuredEmails =3D new Array()=0A= =0A= if (! unObscuredEmails[className])=0A= {=0A= =0A= var elmnts =3D document.getElementsByTagName("span")=0A= for (var i =3D 0, len =3D elmnts.length; 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