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 ORCID: https://orcid.org/0000-0002-7571-6025, Robinson, Sophie, Ware, Victoria Lesley, Brennan, Paul ORCID: https://orcid.org/0000-0001-8792-0499, Thomas, N. Shaun B., Yallop, Deborah, Devereux, Stephen, Fegan, Christopher D. ORCID: https://orcid.org/0000-0001-9685-0621, 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:	24 Oct 2022 09:57
URI:	https://orca.cardiff.ac.uk/id/eprint/42678

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