CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies.
Established cell lines are utilized extensively to study tumor biology and preclinical therapeutic development. However, they may not accurately recapitulate the heterogeneity of their corresponding primary disease. B-cell tumor cells are especially difficult to maintain under conventional culture conditions, limiting access to samples that faithfully represent this disease for preclinical studies. Here, we used primary canine diffuse large B-cell lymphoma to establish a culture system that reliably supports the growth of these cells. CD40 ligand, either expressed by feeder cells or provided as a soluble two-trimeric form, was sufficient to support primary lymphoma cells in vitro. The tumor cells retained their original phenotype, clonality and known karyotypic abnormalities after extended expansion in culture. Finally, we illustrate the utility of the feeder cell-free culture system for comparable assessment of cytotoxicity using dog and human B-cell malignancies. We conclude that this system has broad applications for in vitro preclinical development for B-cell malignancies.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 5455, USA. itoxx018@umn.edu
Daisuke
D
Ito
Aric M
AM
Frantz
Christina
C
Williams
Rachael
R
Thomas
Robert C
RC
Burnett
Anne C
AC
Avery
Matthew
M
Breen
Nicola J
NJ
Mason
Timothy D
TD
O'Brien
Jaime F
JF
Modiano
D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D061252:Feeder Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D023201:CD40 Ligand