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Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells

Hamilton, Emma, Pearce, Laurence, Morgan, Liam, Robinson, Sophie, Ware, Victoria Lesley, Brennan, Paul, Thomas, N. Shaun B., Yallop, Deborah, Devereux, Stephen, Fegan, Christopher D., Buggins, Andrea G. S. and Pepper, Christopher John 2012. Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells. British Journal of Haematology 158 (5) , pp. 589-599. 10.1111/j.1365-2141.2012.09191.x

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Abstract

Interactions in the tumour microenvironment can promote chronic lymphocytic leukaemia (CLL) cell survival, proliferation and drug resistance. A detailed comparison of three co-culture systems designed to mimic the CLL lymph node and vascular microenvironments were performed; two were mouse fibroblast cell lines transfected with human CD40LG or CD31 and the third was a human microvascular endothelial cell line, HMEC-1. All three co-culture systems markedly enhanced CLL cell survival and induced a consistent change in CLL cell phenotype, characterized by increased expression of CD38, CD69, CD44 and ITGA4 (CD49d); this phenotype was absent following co-culture on untransfected mouse fibroblasts. In contrast to HMEC-1 cells, the CD40LG and CD31-expressing fibroblasts also induced ZAP70 expression and marked CLL cell proliferation as evidenced by carboxyfluorescein succinimidyl ester labelling and increased Ki- 67 expression. Taken together, our data show that co-culture on different stroma induced a remarkably similar activation phenotype in CLL cells but only the CD40LG and CD31-expressing fibroblasts increased ZAP70 expression and CLL cell proliferation, indicating that ZAP70 may play a critical role in this process. This comparative study reveals a number of striking similarities between the co-culture systems tested but also highlights important differences that should be considered when selecting which system to use for in-vitro investigations.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: chronic lymphocytic leukaemia, microenvironment, proliferation, survival, co-culture systems
Publisher: Wiley-Blackwell
ISSN: 0007-1048
Last Modified: 13 Jan 2018 20:51
URI: http://orca-mwe.cf.ac.uk/id/eprint/42678

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