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Tumor Biology

Abstract 1114: Upregulation of ALCAM is a marker for non-small-cell lung cancer brain metastases

Desiree Loreth, Justine Münsterberg, Cecile Maire, Stefan Werner, Monja Gandrass, Christian Bernreuther, Jolanthe Kropidlowski, Manfred Westphal, Stefan Steurer, Katrin Lamszus, Markus Glatzel, Klaus Pantel and Harriet Wikman
Desiree Loreth
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Justine Münsterberg
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Cecile Maire
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Stefan Werner
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Monja Gandrass
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Christian Bernreuther
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Jolanthe Kropidlowski
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Manfred Westphal
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Stefan Steurer
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Katrin Lamszus
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Markus Glatzel
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Klaus Pantel
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Harriet Wikman
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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DOI: 10.1158/1538-7445.AM2019-1114 Published July 2019
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Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA

Abstract

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related death with still a 5-year survival rate of <10%. Every second patient with advanced NSCLC will develop brain metastases and in 50% of those the brain is the only site of tumor relapse (oligo-metastasis). Cancer cells need to have specific properties to access and colonize the brain microenvironment leading to the question which metastatic factors foster brain metastasis formation. Different cell adhesion molecules (CAMs) have been shown to be involved in the process of metastasis in different tumor entities. The activated leukocyte cell adhesion molecule (ALCAM) is a type I transmembrane protein of the immunoglobulin superfamily and involved in the maintenance of cell-cell contacts and has a possible role in the “homing” of metastatic cells in distant organs. ALCAM is also involved in the leukocyte transmigration across the blood-brain barrier. Here we therefore investigated the role of ALCAM in NSCLC brain metastases formation. Our studies on patient material revealed that the ALCAM protein expression in brain metastases (n=71) is significantly increased (50.7% positive, p=0.023) compared to the primary tumor (21.7% positive, n=47). Analysis of matched pairs of primary tumors and brain metastases confirmed this observation, as in 33% a de novo ALCAM expression in the matching brain metastases could be observed. Additionally, patients with a strong ALCAM expression in either their primary tumors or brain metastases showed a significantly shortened overall survival (p=0.017 and p=0.035 respectively). In vitro analysis of the effect of ALCAM knock out in the H460 lung cancer cell line showed no effect on proliferation, migration or colony-forming behavior. However, cell adhesion was severely hampered in the knock out cells. Currently in vivo mice experiments are running. Together these findings indicate an important role for ALCAM in brain metastasis formation.

Citation Format: Desiree Loreth, Justine Münsterberg, Cecile Maire, Stefan Werner, Monja Gandrass, Christian Bernreuther, Jolanthe Kropidlowski, Manfred Westphal, Stefan Steurer, Katrin Lamszus, Markus Glatzel, Klaus Pantel, Harriet Wikman. Upregulation of ALCAM is a marker for non-small-cell lung cancer brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1114.

  • ©2019 American Association for Cancer Research.
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Cancer Research: 79 (13 Supplement)
July 2019
Volume 79, Issue 13 Supplement
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Abstract 1114: Upregulation of ALCAM is a marker for non-small-cell lung cancer brain metastases
Desiree Loreth, Justine Münsterberg, Cecile Maire, Stefan Werner, Monja Gandrass, Christian Bernreuther, Jolanthe Kropidlowski, Manfred Westphal, Stefan Steurer, Katrin Lamszus, Markus Glatzel, Klaus Pantel and Harriet Wikman
Cancer Res July 1 2019 (79) (13 Supplement) 1114; DOI: 10.1158/1538-7445.AM2019-1114

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Abstract 1114: Upregulation of ALCAM is a marker for non-small-cell lung cancer brain metastases
Desiree Loreth, Justine Münsterberg, Cecile Maire, Stefan Werner, Monja Gandrass, Christian Bernreuther, Jolanthe Kropidlowski, Manfred Westphal, Stefan Steurer, Katrin Lamszus, Markus Glatzel, Klaus Pantel and Harriet Wikman
Cancer Res July 1 2019 (79) (13 Supplement) 1114; DOI: 10.1158/1538-7445.AM2019-1114
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