Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization
Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is know...
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| Veröffentlicht in: | Clinical & experimental metastasis 2008-11, Vol.25 (7), p.799-810 |
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| creator | Fitzgerald, Daniel P. Palmieri, Diane Hua, Emily Hargrave, Elizabeth Herring, Jeanne M. Qian, Yongzhen Vega-Valle, Eleazar Weil, Robert J. Stark, Andreas M. Vortmeyer, Alexander O. Steeg, Patricia S. |
| description | Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (~50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a ~5-fold increase in metastatic cell proliferation (
P
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| doi_str_mv | 10.1007/s10585-008-9193-z |
| format | Article |
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P
< 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.</description><identifier>ISSN: 0262-0898</identifier><identifier>EISSN: 1573-7276</identifier><identifier>EISSN: 1473-7276</identifier><identifier>DOI: 10.1007/s10585-008-9193-z</identifier><identifier>PMID: 18649117</identifier><identifier>CODEN: CEXMD2</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adult ; Aged ; Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Brain Neoplasms - secondary ; Breast Neoplasms - pathology ; Cancer Research ; CD11b Antigen - analysis ; Cell Movement ; Cell Proliferation ; Female ; Hematology ; Humans ; Leukocyte Common Antigens - analysis ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neuroglia - physiology ; Oncology ; Research Paper ; Surgical Oncology</subject><ispartof>Clinical & experimental metastasis, 2008-11, Vol.25 (7), p.799-810</ispartof><rights>Springer Science+Business Media B.V. 2008</rights><rights>Springer Science+Business Media B.V. 2008 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-a131d7a2b138c34d3fb89ea552a0393a4d9c833a5a08f6be45452122146526d83</citedby><cites>FETCH-LOGICAL-c564t-a131d7a2b138c34d3fb89ea552a0393a4d9c833a5a08f6be45452122146526d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10585-008-9193-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10585-008-9193-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18649117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fitzgerald, Daniel P.</creatorcontrib><creatorcontrib>Palmieri, Diane</creatorcontrib><creatorcontrib>Hua, Emily</creatorcontrib><creatorcontrib>Hargrave, Elizabeth</creatorcontrib><creatorcontrib>Herring, Jeanne M.</creatorcontrib><creatorcontrib>Qian, Yongzhen</creatorcontrib><creatorcontrib>Vega-Valle, Eleazar</creatorcontrib><creatorcontrib>Weil, Robert J.</creatorcontrib><creatorcontrib>Stark, Andreas M.</creatorcontrib><creatorcontrib>Vortmeyer, Alexander O.</creatorcontrib><creatorcontrib>Steeg, Patricia S.</creatorcontrib><title>Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization</title><title>Clinical & experimental metastasis</title><addtitle>Clin Exp Metastasis</addtitle><addtitle>Clin Exp Metastasis</addtitle><description>Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (~50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a ~5-fold increase in metastatic cell proliferation (
P
< 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain Neoplasms - secondary</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer Research</subject><subject>CD11b Antigen - analysis</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Leukocyte Common Antigens - analysis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Middle Aged</subject><subject>Neuroglia - physiology</subject><subject>Oncology</subject><subject>Research Paper</subject><subject>Surgical Oncology</subject><issn>0262-0898</issn><issn>1573-7276</issn><issn>1473-7276</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUuLFDEUhYMoTtv6A9xIcOGuNO_HRpBhHIUBQXQdUqlb3RmqKm1SNdD9601PN44KIgRCcr9zbm4OQi8peUsJ0e8KJdLIhhDTWGp5c3iEVlRq3mim1WO0IkyxhhhrLtCzUm4JIUJr8xRdUKOEpVSv0P4r-DDHO8CbIXrsM-AMIS9xhg63e7yNm-2wx7uchthD9vdom32c8AizL3VBwamvd1BPOPgpQMZ-6o6aMc2A52VMGQcYBhzSkKZ4qC5peo6e9H4o8OK8r9H3j1ffLj81N1-uP19-uGmCVGJuPOW00561lJvARcf71ljwUjJPuOVedDYYzr30xPSqBSGFZJQxKpRkqjN8jd6ffHdLO0IXYJqzH9wux9HnvUs-uj8rU9y6TbpzTGnLLa0Gb84GOf1YoMxujOU4jp8gLcUpqzijnP0XZJQIQrms4Ou_wNu05Kn-QmUE1ZrVENeInqCQUykZ-l9PpsQd43en-F2N3x3jd4eqefX7rA-Kc94VYCeg1NK0gfzQ-d-uPwFp3b3D</recordid><startdate>20081101</startdate><enddate>20081101</enddate><creator>Fitzgerald, Daniel P.</creator><creator>Palmieri, Diane</creator><creator>Hua, Emily</creator><creator>Hargrave, Elizabeth</creator><creator>Herring, Jeanne M.</creator><creator>Qian, Yongzhen</creator><creator>Vega-Valle, Eleazar</creator><creator>Weil, Robert J.</creator><creator>Stark, Andreas M.</creator><creator>Vortmeyer, Alexander O.</creator><creator>Steeg, Patricia S.</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081101</creationdate><title>Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization</title><author>Fitzgerald, Daniel P. ; Palmieri, Diane ; Hua, Emily ; Hargrave, Elizabeth ; Herring, Jeanne M. ; Qian, Yongzhen ; Vega-Valle, Eleazar ; Weil, Robert J. ; Stark, Andreas M. ; Vortmeyer, Alexander O. ; Steeg, Patricia S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-a131d7a2b138c34d3fb89ea552a0393a4d9c833a5a08f6be45452122146526d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical & experimental metastasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fitzgerald, Daniel P.</au><au>Palmieri, Diane</au><au>Hua, Emily</au><au>Hargrave, Elizabeth</au><au>Herring, Jeanne M.</au><au>Qian, Yongzhen</au><au>Vega-Valle, Eleazar</au><au>Weil, Robert J.</au><au>Stark, Andreas M.</au><au>Vortmeyer, Alexander O.</au><au>Steeg, Patricia S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization</atitle><jtitle>Clinical & experimental metastasis</jtitle><stitle>Clin Exp Metastasis</stitle><addtitle>Clin Exp Metastasis</addtitle><date>2008-11-01</date><risdate>2008</risdate><volume>25</volume><issue>7</issue><spage>799</spage><epage>810</epage><pages>799-810</pages><issn>0262-0898</issn><eissn>1573-7276</eissn><eissn>1473-7276</eissn><coden>CEXMD2</coden><abstract>Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a “sanctuary” site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (~50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a ~5-fold increase in metastatic cell proliferation (
P
< 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>18649117</pmid><doi>10.1007/s10585-008-9193-z</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical & experimental metastasis, 2008-11, Vol.25 (7), p.799-810 |
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| subjects | Adult Aged Animals Apoptosis Biomedical and Life Sciences Biomedicine Brain Neoplasms - secondary Breast Neoplasms - pathology Cancer Research CD11b Antigen - analysis Cell Movement Cell Proliferation Female Hematology Humans Leukocyte Common Antigens - analysis Mice Mice, Inbred BALB C Middle Aged Neuroglia - physiology Oncology Research Paper Surgical Oncology |
| title | Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization |
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