Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 186, Issue 8, Pages 2171-2182Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.04.003
Keywords
-
Categories
Funding
- Spanish Myeloma Network Program [RD12/0036/0058]
- Spanish Association for Cancer Research [GCB120981SAN]
- INNOCAMPUS Program [CEI10-1-0010]
- Spanish MINECO-ISCIII [PI12/02591]
- FEDER
- Consejeria de Educacion from Junta Castilla y Leon [FIC335U14]
- Centers for Regenerative Medicine and Cellular Therapy from Castilla y Leon
Ask authors/readers for more resources
IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herein, we investigated the sources of IL-8 production in multiple myeloma (MM) and its potential roles in MM pathogenesis. We found that bone marrow cells from patients with MM secreted higher amounts of IL-8 than healthy donors. IL-8 production was detected in cultures of CD138+ plasma cells and CD138(-) cells isolated from bone marrows of MM patients, and in three of seven human myeloma cell lines (HMCLs) analyzed. Interactions between MM and stromal cells increased IL-8 secretion by stromal cells through cell-cell adhesion and soluble factors. Interestingly, 1L8 expression also increased in HMCLs, stromal cells, and osteoclasts after treatment with the antimyeloma drugs melphalan and bortezomib. In fact, the effect of bortezomib on IL-8 production was higher than that exerted by stromal-MM cell interactions. Addition of exogenous IL-8 did not affect growth of HMCLs, although it protected cells from death induced by serum starvation through a caspase-independent mechanism. Furthermore, IL-8 induced by stromal-MM cell interactions strongly contributed to osteoclast formation in vitro, because osteoclastogenesis was markedly reduced by IL-8 specific neutralizing antibodies. In conclusion, our results implicate IL-8 in myeloma bone disease and point to the potential utility of an anti IL-8 therapy to prevent unwanted effects of IL-8 up-regulation on survival, angiogenesis, and osteolysis in MM.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available