Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells < em > in vivo < /em > .

Expression of the chemokine receptor CCR1 promotes the dissemination of multiple myeloma plasma cells <em>in vivo</em>.
Haematologica. 2020 Nov 05;Online ahead of print:0
Authors: Zeissig MN, Hewett DR, Panagopoulos V, Mrozik KM, To LB, Croucher PI, Zannettino ACW, Vandyke K
Abstract
Multiple myeloma (MM) disease progression is dependent on the ability of MM plasma cells (PCs) to egress from the bone marrow (BM), enter the circulation and disseminate to distal BM sites. Expression of the chemokine CXCL12 by BM stromal cells is crucial for MM PC retention within the BM. However, the mechanisms which overcome CXCL12-mediated retention to enable dissemination are poorly understood. We have previously identified that treatment with the CCR1 ligand CCL3 inhibits the response to CXCL12 in MM cell lines, suggesting that CCL3/CCR1 signalling may enable egress of MM PC from the BM. Here, we demonstrated that CCR1 expression was an independent prognostic indicator in newly diagnosed MM patients. Furthermore, we showed that CCR1 is a crucial driver of dissemination in vivo, with CCR1 expression in the murine MM cell line 5TGM1 being associated with an increased incidence of bone and splenic disseminated tumours in C57BL/KaLwRij mice. Furthermore, we demonstrated that CCR1 knockout in the human myeloma cell line OPM2 resulted in a >95% reduction in circulating MM PC numbers and BM and splenic tumour dissemination following intrati...

Source: Haematologica - November 5, 2020 Category: Hematology Authors: Zeissig MN, Hewett DR, Panagopoulos V, Mrozik KM, To LB, Croucher PI, Zannettino ACW, Vandyke K Tags: Haematologica Source Type: research