TITLE:
Autocrine Production of Interleukin-6: A Mechanism of Interleukin-6 Independence in Dexamethasone-Resistant 7TD1 Murine Myeloma Cells
AUTHORS:
Kalyan J. Gangavarapu, Alok Bhushan, James C. K. Lai, Christopher K. Daniels
KEYWORDS:
Multiple Myeloma, Interleukin-6, 7TD1 Cells, Autocrine Production, Dexamethasone Resistance
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.6,
May
16,
2014
ABSTRACT: Several factors could
contribute to proliferation of multiple myeloma (MM) cells independent of
interleukin-6 (IL6) in the later stages of the disease. Our previous studies
established a dexamethasone-resistant 7TD1 cell line (7TD1-Dxm) and have shown
that one mechanism of resistance to dexamethasone is due to inhibition of
cytochrome c release. We have also observed that 7TD1-Dxm cells proliferate independently
of externally-added IL6. This study therefore aimed to elucidate the mechanisms
responsible for IL6-independent proliferation in 7TD1-Dxm cells. Our results
indicated that 7TD1-Dxm cells produced IL6 in an autocrine fashion. We have
observed that dexamethasone-resistant 7TD1 cells become dexamethasone-resistant
and IL6-independent for proliferation concomitantly. This strongly suggests
that production of IL6 by 7TD1-Dxm cells may play an important role in the
development of dexamethasone resistance. Consequently, further investigation of
the molecular mechanisms responsible for IL6 production may be helpful in
delineating the mechanisms leading to dexamethasone resistance.