Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule
Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Ove...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2008-05, Vol.68 (10), p.3671-3679 |
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creator | van Kilsdonk, Jeroen W J Wilting, Roel H Bergers, Mieke van Muijen, Goos N P Schalkwijk, Joost van Kempen, Léon C L T Swart, Guido W M |
description | Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Overexpression of sALCAM in metastatic melanoma cells disturbed clustering of endogenous ALCAM and inhibited activation of matrix metalloproteinase-2 (MMP-2). Exposure of HT1080 fibrosarcoma cells to sALCAM similarly inhibited MMP-2, suggesting a broader effect on ALCAM-positive tumor cells. In contrast to the previously reported, promotive effects of an NH(2)-terminally truncated, transmembrane variant (DeltaN-ALCAM), sALCAM impaired the migratory capacity of transfected cells in vitro, reduced basement membrane penetration in reconstituted human skin equivalents, and diminished metastatic capacity in nude mice. Remarkably, L1 neuronal cell adhesion molecule (L1CAM/CD171), another progression marker of several cancers including melanoma, was suppressed upon sALCAM overexpression but was up-regulated by DeltaN-ALCAM. The partially overlapping and opposite effects induced by alternative strategies targeting ALCAM functions collectively attribute an integrative role to ALCAM in orchestrating cell adhesion, growth, invasion, and proteolysis in the tumor tissue microenvironment and disclose a therapeutic potential for sALCAM. |
doi_str_mv | 10.1158/0008-5472.CAN-07-5767 |
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We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Overexpression of sALCAM in metastatic melanoma cells disturbed clustering of endogenous ALCAM and inhibited activation of matrix metalloproteinase-2 (MMP-2). Exposure of HT1080 fibrosarcoma cells to sALCAM similarly inhibited MMP-2, suggesting a broader effect on ALCAM-positive tumor cells. In contrast to the previously reported, promotive effects of an NH(2)-terminally truncated, transmembrane variant (DeltaN-ALCAM), sALCAM impaired the migratory capacity of transfected cells in vitro, reduced basement membrane penetration in reconstituted human skin equivalents, and diminished metastatic capacity in nude mice. Remarkably, L1 neuronal cell adhesion molecule (L1CAM/CD171), another progression marker of several cancers including melanoma, was suppressed upon sALCAM overexpression but was up-regulated by DeltaN-ALCAM. The partially overlapping and opposite effects induced by alternative strategies targeting ALCAM functions collectively attribute an integrative role to ALCAM in orchestrating cell adhesion, growth, invasion, and proteolysis in the tumor tissue microenvironment and disclose a therapeutic potential for sALCAM.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-07-5767</identifier><identifier>PMID: 18483249</identifier><language>eng</language><publisher>United States</publisher><subject>Activated-Leukocyte Cell Adhesion Molecule - chemistry ; Animals ; Basement Membrane - metabolism ; Cell Adhesion ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Leukocytes - cytology ; Melanoma - pathology ; Melanoma - therapy ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neural Cell Adhesion Molecule L1 - metabolism ; Protein Structure, Tertiary</subject><ispartof>Cancer research (Chicago, Ill.), 2008-05, Vol.68 (10), p.3671-3679</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-9bc4595912dc7d149d9515c91cd03ffcc69cc7bad5caa1e8ac0a13f5c32f11c13</citedby><cites>FETCH-LOGICAL-c454t-9bc4595912dc7d149d9515c91cd03ffcc69cc7bad5caa1e8ac0a13f5c32f11c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18483249$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Kilsdonk, Jeroen W J</creatorcontrib><creatorcontrib>Wilting, Roel H</creatorcontrib><creatorcontrib>Bergers, Mieke</creatorcontrib><creatorcontrib>van Muijen, Goos N P</creatorcontrib><creatorcontrib>Schalkwijk, Joost</creatorcontrib><creatorcontrib>van Kempen, Léon C L T</creatorcontrib><creatorcontrib>Swart, Guido W M</creatorcontrib><title>Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Overexpression of sALCAM in metastatic melanoma cells disturbed clustering of endogenous ALCAM and inhibited activation of matrix metalloproteinase-2 (MMP-2). Exposure of HT1080 fibrosarcoma cells to sALCAM similarly inhibited MMP-2, suggesting a broader effect on ALCAM-positive tumor cells. In contrast to the previously reported, promotive effects of an NH(2)-terminally truncated, transmembrane variant (DeltaN-ALCAM), sALCAM impaired the migratory capacity of transfected cells in vitro, reduced basement membrane penetration in reconstituted human skin equivalents, and diminished metastatic capacity in nude mice. Remarkably, L1 neuronal cell adhesion molecule (L1CAM/CD171), another progression marker of several cancers including melanoma, was suppressed upon sALCAM overexpression but was up-regulated by DeltaN-ALCAM. The partially overlapping and opposite effects induced by alternative strategies targeting ALCAM functions collectively attribute an integrative role to ALCAM in orchestrating cell adhesion, growth, invasion, and proteolysis in the tumor tissue microenvironment and disclose a therapeutic potential for sALCAM.</description><subject>Activated-Leukocyte Cell Adhesion Molecule - chemistry</subject><subject>Animals</subject><subject>Basement Membrane - metabolism</subject><subject>Cell Adhesion</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Leukocytes - cytology</subject><subject>Melanoma - pathology</subject><subject>Melanoma - therapy</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neural Cell Adhesion Molecule L1 - metabolism</subject><subject>Protein Structure, Tertiary</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPwzAQhC0EoqXwE0A5cUuxa7uOj1XFS6rgAmdrs96IQB4ldir135PQCk6rHc3srD7GrgWfC6GzO855lmplFvP16iXlJtVmaU7YVGiZpUYpfcqmf54Juwjhc1i14PqcTUSmMrlQdsr8KkZqeohl2yRtkdRUQdPWkJTNDsIo5vsEkkDYUSSf7KAroYmjFTCWOxjFivqvFveREqSqSsB_0G-0bivCvqJLdlZAFejqOGfs_eH-bf2Ubl4fn9erTYpKq5jafJhWW7HwaLxQ1lstNFqBnsuiQFxaRJOD1wggKAPkIGShUS4KIVDIGbs93N127XdPIbq6DONL0FDbB2e4GYoyORj1wYhdG0JHhdt2ZQ3d3gnuRrxuROdGdG7A67hxI94hd3Ms6POa_H_qyFP-AP1UeHg</recordid><startdate>20080515</startdate><enddate>20080515</enddate><creator>van Kilsdonk, Jeroen W J</creator><creator>Wilting, Roel H</creator><creator>Bergers, Mieke</creator><creator>van Muijen, Goos N P</creator><creator>Schalkwijk, Joost</creator><creator>van Kempen, Léon C L T</creator><creator>Swart, Guido W M</creator><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>7X8</scope></search><sort><creationdate>20080515</creationdate><title>Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule</title><author>van Kilsdonk, Jeroen W J ; Wilting, Roel H ; Bergers, Mieke ; van Muijen, Goos N P ; Schalkwijk, Joost ; van Kempen, Léon C L T ; Swart, Guido W M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-9bc4595912dc7d149d9515c91cd03ffcc69cc7bad5caa1e8ac0a13f5c32f11c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Activated-Leukocyte Cell Adhesion Molecule - chemistry</topic><topic>Animals</topic><topic>Basement Membrane - metabolism</topic><topic>Cell Adhesion</topic><topic>Cell Line, Tumor</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Leukocytes - cytology</topic><topic>Melanoma - pathology</topic><topic>Melanoma - therapy</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Neural Cell Adhesion Molecule L1 - metabolism</topic><topic>Protein Structure, Tertiary</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Kilsdonk, Jeroen W J</creatorcontrib><creatorcontrib>Wilting, Roel H</creatorcontrib><creatorcontrib>Bergers, Mieke</creatorcontrib><creatorcontrib>van Muijen, Goos N P</creatorcontrib><creatorcontrib>Schalkwijk, Joost</creatorcontrib><creatorcontrib>van Kempen, Léon C L T</creatorcontrib><creatorcontrib>Swart, Guido W M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Kilsdonk, Jeroen W J</au><au>Wilting, Roel H</au><au>Bergers, Mieke</au><au>van Muijen, Goos N P</au><au>Schalkwijk, Joost</au><au>van Kempen, Léon C L T</au><au>Swart, Guido W M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2008-05-15</date><risdate>2008</risdate><volume>68</volume><issue>10</issue><spage>3671</spage><epage>3679</epage><pages>3671-3679</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><abstract>Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration. Overexpression of sALCAM in metastatic melanoma cells disturbed clustering of endogenous ALCAM and inhibited activation of matrix metalloproteinase-2 (MMP-2). Exposure of HT1080 fibrosarcoma cells to sALCAM similarly inhibited MMP-2, suggesting a broader effect on ALCAM-positive tumor cells. In contrast to the previously reported, promotive effects of an NH(2)-terminally truncated, transmembrane variant (DeltaN-ALCAM), sALCAM impaired the migratory capacity of transfected cells in vitro, reduced basement membrane penetration in reconstituted human skin equivalents, and diminished metastatic capacity in nude mice. Remarkably, L1 neuronal cell adhesion molecule (L1CAM/CD171), another progression marker of several cancers including melanoma, was suppressed upon sALCAM overexpression but was up-regulated by DeltaN-ALCAM. 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subjects | Activated-Leukocyte Cell Adhesion Molecule - chemistry Animals Basement Membrane - metabolism Cell Adhesion Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Leukocytes - cytology Melanoma - pathology Melanoma - therapy Mice Mice, Nude Neoplasm Invasiveness Neoplasm Metastasis Neural Cell Adhesion Molecule L1 - metabolism Protein Structure, Tertiary |
title | Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule |
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