The malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma are surrounded by a tumour microenvironment which is composed of a variety of cell types, as well as non-cellular components such as collagen. Although HRS cells harbour oncogenic Epstein-Barr virus (EBV) in approximately 50% of cases, it is not known if the tumour microenvironment contributes to EBV-driven lymphomagenesis. We show that expression of the EBV-encoded latent membrane protein-1 (LMP1) in primary human germinal centre B cells, the presumed progenitors of HRS cells, up-regulates discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen. We show that HRS cells intimately associated with collagen frequently over-express DDR1 and that short-term exposure to collagen is sufficient to activate DDR1 in Hodgkin lymphoma-derived cell lines. We also show that ectopic expression of DDR1 significantly increased the survival of collagen-treated DG75, Burkitt lymphoma cells, following etoposide treatment. Conversely, inhibition of DDR1, by RNA interference, significantly decreased the survival of collagen-treated L428 Hodgkin lymphoma cells in the absence of specific apoptotic stimulus suggesting that DDR1 also influences baseline survival. Our results identify a hitherto unknown function for collagen in protecting Hodgkin lymphoma from apoptosis and suggest an important contribution of the tumour microenvironment in promoting the oncogenic effects of EBV.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.