Document Detail

Constitutive integrin activation on tumor cells contributes to progression of leptomeningeal metastases.
MedLine Citation:
PMID:  16533879     Owner:  NLM     Status:  MEDLINE    
Leptomeningeal metastases are a serious neurological complication in cancer patients and associated with a dismal prognosis. Tumor cells that enter the subarachnoid space adhere to the leptomeninges and form tumor deposits. It is largely unknown which adhesion molecules mediate tumor cell adhesion to leptomeninges. We studied the role of integrin expression and activation in the progression of leptomeningeal metastases. For this study, we used a mouse acute lymphocytic leukemic cell line that was grown in suspension (L1210-S cell line) to develop an adherent L1210 cell line (L1210-A) by selectively culturing the few adherent cells in the cell culture. beta1, beta2, and beta3 integrins were in a constitutively high active state on L1210-A cells and in a low, but inducible, active state on L1210-S cells. Expression levels of these integrins were comparable in the two cell lines. Static adhesion levels of L1210-A cells on a leptomeningeal cell layer were significantly higher than those of L1210-S cells. All mice that were injected intrathecally with L1210-A cells died rapidly of leptomeningeal leukemia. In contrast, 45% long-term survival was seen after intrathecal injection of mice with L1210-S cells. Our data indicate that constitutive integrin activation on leukemic cells promotes progression of leptomeningeal leukemia by increased tumor cell adhesion to the leptomeninges. We argue that an aberrantly regulated inside-out signaling pathway underlies constitutive integrin activation on the adherent leukemic cell population.
Dieta Brandsma; Laurien Ulfman; Jaap C Reijneveld; Madelon Bracke; Martin J B Taphoorn; Jaap Jan Zwaginga; Martijn F B Gebbink; Hetty de Boer; Leo Koenderman; Emile E Voest
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-13
Journal Detail:
Title:  Neuro-oncology     Volume:  8     ISSN:  1522-8517     ISO Abbreviation:  Neuro-oncology     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-06     Completed Date:  2006-06-02     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100887420     Medline TA:  Neuro Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  127-36     Citation Subset:  IM    
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
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MeSH Terms
Cell Adhesion / physiology
Cell Line, Tumor
Disease Progression
Integrins / metabolism*
Meningeal Neoplasms / metabolism*,  secondary*
Mice, Inbred DBA
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
Reg. No./Substance:

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