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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31239322</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>07</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1557-3265</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>18</Issue><PubDate><Year>2019</Year><Month>Sep</Month><Day>15</Day></PubDate></JournalIssue><Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title><ISOAbbreviation>Clin Cancer Res</ISOAbbreviation></Journal><ArticleTitle>VEGFR1<sup>+</sup> Metastasis-Associated Macrophages Contribute to Metastatic Angiogenesis and Influence Colorectal Cancer Patient Outcome.</ArticleTitle><Pagination><StartPage>5674</StartPage><EndPage>5685</EndPage><MedlinePgn>5674-5685</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1158/1078-0432.CCR-18-2123</ELocationID><Abstract><AbstractText Label="PURPOSE">To investigate the clinical relevance of macrophages in liver metastasis of colorectal cancer and their influence on angiogenesis and patient survival. Moreover to evaluate specific blood monocytes as markers of disease recurrence.<b>Experimental design:</b> In a mouse model with spontaneous liver metastasis, the angiogenic characteristics of tumor- and metastasis (MAM)-associated macrophages were evaluated. Macrophages and the vasculature from 130 primary tumor (pTU) and 123 patients with liver metastasis were assessed. <i>In vivo</i> and in human samples, the clinical relevance of macrophage VEGFR1 expression was analyzed. Blood samples from patients (<i>n</i> = 157, 80 pTU and 77 liver metastasis) were analyzed for assessing VEGFR1-positive (VEGFR1<sup>+</sup>) cells as suitable biomarkers of disease recurrence.</AbstractText><AbstractText Label="RESULTS">The number of macrophages positively correlated with vascularization in metastasis. Both in the murine model as well as in primary isolated human cells, a subpopulation of MAMs expressing VEGFR1 were found highly angiogenic. While VEGFR1 expression in pTU patients did not predict prognosis; high percentage of VEGFR1<sup>+</sup> cells in liver metastasis was associated with worse patient outcome. Interestingly, VEGFR1<sup>+</sup>-circulating monocytes in blood samples from patients with liver metastasis not only predicted progression but also site of recurrence.</AbstractText><AbstractText Label="CONCLUSIONS">Our findings identify a new subset of proangiogenic VEGFR1<sup>+</sup> MAMs in colorectal cancer that support metastatic growth and may become a liquid biomarker to predict disease recurrence in the liver.</AbstractText><CopyrightInformation>&#xa9;2019 American Association for Cancer Research.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Freire Valls</LastName><ForeName>Aida</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biochemistry Center Heidelberg (BZH), Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Knipper</LastName><ForeName>Karl</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giannakouri</LastName><ForeName>Evangelia</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sarachaga</LastName><ForeName>V&#xed;ctor</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Biochemistry Center Heidelberg (BZH), Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hinterkopf</LastName><ForeName>Sascha</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-5371-5737</Identifier><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wuehrl</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Radhakrishnan</LastName><ForeName>Praveenkumar</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Klose</LastName><ForeName>Johannes</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ulrich</LastName><ForeName>Alexis</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Augustin</LastName><ForeName>Hellmut G</ForeName><Initials>HG</Initials><Identifier Source="ORCID">0000-0002-7173-4242</Identifier><AffiliationInfo><Affiliation>Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruiz de Almodovar</LastName><ForeName>Carmen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Biochemistry Center Heidelberg (BZH), Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><Identifier Source="ORCID">0000-0002-7166-3675</Identifier><AffiliationInfo><Affiliation>Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany. thomas1.schmidt@med.uni-heidelberg.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Clin Cancer Res</MedlineTA><NlmUniqueID>9502500</NlmUniqueID><ISSNLinking>1078-0432</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014408">Biomarkers, Tumor</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C572548">FITM1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D040281">Vascular Endothelial Growth Factor Receptor-1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014408" MajorTopicYN="N">Biomarkers, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015179" MajorTopicYN="N">Colorectal Neoplasms</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005455" MajorTopicYN="N">Fluorescent Antibody Technique</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008113" MajorTopicYN="N">Liver Neoplasms</DescriptorName><QualifierName UI="Q000556" MajorTopicYN="N">secondary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008565" MajorTopicYN="N">Membrane Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011379" MajorTopicYN="N">Prognosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012008" MajorTopicYN="N">Recurrence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D040281" MajorTopicYN="N">Vascular Endothelial Growth Factor Receptor-1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D023041" MajorTopicYN="N">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>7</Month><Day>4</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>5</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>6</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>6</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>6</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31239322</ArticleId><ArticleId IdType="doi">10.1158/1078-0432.CCR-18-2123</ArticleId><ArticleId IdType="pii">1078-0432.CCR-18-2123</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>