An analysis of the role of follicular lymphoma-associated fibroblasts to promote tumor cell viability following drug-induced apoptosis

Abstract

Treatment response of follicular lymphomas (FL) is highly variable. We, therefore, investigated the role of FL cancer-associated fibroblasts (CAFs) on tumor cell viability, in particular in response to treatment with cytotoxic drugs. Stromal cells outgrown from FL patients were characterized and pure CAF populations were co-cultivated with FL cells. To analyze fibroblast-mediated effects, cells in co-culture were treated with ABT-737 and Bortezomib. The adherent cell population was positive for all fibroblastic markers tested and showed increased mRNA-expression of the activation marker FAP. No effect on FL cell viability was noted when co-cultivating them with CAFs. However, stromal cells protected tumor cells from apoptosis in response to cytotoxic treatment. This might be explained by mRNA-induction of ABCC1 and ABCG2 and up-regulation of BCL2L1 in FL cells. Our finding of protective mechanisms mediated by CAFs is of pivotal impact for further studies of cytotoxic agents in FL.

Keywords:

• Follicular lymphoma
• cancer-associated fibroblast
• co-cultivation
• CD20
• apoptosis

Acknowledgements

We gratefully acknowledge Petra Hitschke, Katja Bräutigam, Daniela Rauh and Thomas Hees for excellent technical assistance. This study was supported by the Robert-Bosch-Stiftung (Stuttgart, Germany).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1263841.