Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE...
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| description | Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM. |
| doi_str_mv | 10.1371/journal.pone.0122269 |
| format | Article |
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15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0122269</identifier><identifier>PMID: 25807228</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Adults ; Aged ; Aged, 80 and over ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - metabolism ; Brain ; Brain cancer ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - drug therapy ; Brain Neoplasms - pathology ; Brain tumors ; CD45 antigen ; Cell surface ; Cloning ; Emission analysis ; Endothelial cells ; Female ; Gallium ; Glioblastoma ; Glioblastoma - diagnostic imaging ; Glioblastoma - drug therapy ; Glioblastoma - pathology ; Glioblastoma multiforme ; Glioma ; Glioma cells ; Gliomas ; Growth factors ; Humans ; Immunohistochemistry ; Infiltration ; Leukocyte Common Antigens - metabolism ; Macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Magnetic Resonance Imaging ; Male ; Medical imaging ; Medical prognosis ; Metastases ; Microglia ; Microglial cells ; Middle Aged ; Nervous system ; Neuroimaging ; Neuropathology ; Neurosurgery ; Nuclear medicine ; Organometallic Compounds - chemistry ; Patients ; Peptides ; Positron emission ; Positron emission tomography ; Prognosis ; Radiation therapy ; Radiography ; Receptors, Somatostatin - metabolism ; Retrospective Studies ; Somatostatin ; Somatostatin receptors ; Staining ; Target recognition ; Tomography ; Tracers (Biology) ; Tumor cells ; Tumors</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0122269-e0122269</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Lapa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Lapa et al 2015 Lapa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-315527035e8ed1c7f75762b3c9ed1bfe130411acfb8c1d7aab1b5c71d71a8b423</citedby><cites>FETCH-LOGICAL-c692t-315527035e8ed1c7f75762b3c9ed1bfe130411acfb8c1d7aab1b5c71d71a8b423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373835/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373835/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25807228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lapa, Constantin</creatorcontrib><creatorcontrib>Linsenmann, Thomas</creatorcontrib><creatorcontrib>Lückerath, Katharina</creatorcontrib><creatorcontrib>Samnick, Samuel</creatorcontrib><creatorcontrib>Herrmann, Ken</creatorcontrib><creatorcontrib>Stoffer, Carolin</creatorcontrib><creatorcontrib>Ernestus, Ralf-Ingo</creatorcontrib><creatorcontrib>Buck, Andreas K</creatorcontrib><creatorcontrib>Löhr, Mario</creatorcontrib><creatorcontrib>Monoranu, Camelia-Maria</creatorcontrib><title>Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.</description><subject>Adult</subject><subject>Adults</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>CD45 antigen</subject><subject>Cell surface</subject><subject>Cloning</subject><subject>Emission analysis</subject><subject>Endothelial cells</subject><subject>Female</subject><subject>Gallium</subject><subject>Glioblastoma</subject><subject>Glioblastoma - diagnostic imaging</subject><subject>Glioblastoma - drug therapy</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma multiforme</subject><subject>Glioma</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Infiltration</subject><subject>Leukocyte Common Antigens - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lapa, Constantin</au><au>Linsenmann, Thomas</au><au>Lückerath, Katharina</au><au>Samnick, Samuel</au><au>Herrmann, Ken</au><au>Stoffer, Carolin</au><au>Ernestus, Ralf-Ingo</au><au>Buck, Andreas K</au><au>Löhr, Mario</au><au>Monoranu, Camelia-Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-25</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0122269</spage><epage>e0122269</epage><pages>e0122269-e0122269</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.
15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.
The amount of microglia/macrophages ranged from <10% to >50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.
SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25807228</pmid><doi>10.1371/journal.pone.0122269</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0122269-e0122269 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2041298810 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Adults Aged Aged, 80 and over Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - metabolism Brain Brain cancer Brain Neoplasms - diagnostic imaging Brain Neoplasms - drug therapy Brain Neoplasms - pathology Brain tumors CD45 antigen Cell surface Cloning Emission analysis Endothelial cells Female Gallium Glioblastoma Glioblastoma - diagnostic imaging Glioblastoma - drug therapy Glioblastoma - pathology Glioblastoma multiforme Glioma Glioma cells Gliomas Growth factors Humans Immunohistochemistry Infiltration Leukocyte Common Antigens - metabolism Macrophages Macrophages - immunology Macrophages - metabolism Magnetic Resonance Imaging Male Medical imaging Medical prognosis Metastases Microglia Microglial cells Middle Aged Nervous system Neuroimaging Neuropathology Neurosurgery Nuclear medicine Organometallic Compounds - chemistry Patients Peptides Positron emission Positron emission tomography Prognosis Radiation therapy Radiography Receptors, Somatostatin - metabolism Retrospective Studies Somatostatin Somatostatin receptors Staining Target recognition Tomography Tracers (Biology) Tumor cells Tumors |
| title | Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy? |
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