PMID- 37686623
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230911
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 17
DP  - 2023 Aug 31
TI  - Unlocking Drug Resistance in Multiple Myeloma: Adipocytes as Modulators of 
      Treatment Response.
LID - 10.3390/cancers15174347 [doi]
LID - 4347
AB  - Multiple myeloma (MM) is an incurable hematological malignancy characterized by 
      the clonal proliferation of malignant plasma cells. Despite the development of a 
      diverse array of targeted drug therapies over the last decade, patients often 
      relapse and develop refractory disease due to multidrug resistance. Obesity is a 
      growing public health threat and a risk factor for multiple myeloma, although the 
      mechanisms by which obesity contributes to MM growth and progression have not 
      been fully elucidated. In the present study, we evaluated whether crosstalk 
      between adipocytes and MM cells promoted drug resistance and whether this was 
      amplified by obesity. Human adipose-derived stem cells (ASCs) from nineteen 
      normal (BMI = 20-25 kg/m(2)), overweight (25-30 kg/m(2)), or obese (30-35 
      kg/m(2)) patients undergoing elective liposuction were utilized. Cells were 
      differentiated into adipocytes, co-cultured with RPMI 8226 or U266B1 multiple 
      myeloma cell lines, and treated with standard MM therapies, including bortezomib 
      or a triple combination of bortezomib, dexamethasone, and lenalidomide. We found 
      that adipocytes from overweight and obese individuals increased cell 
      adhesion-mediated drug resistance (CAM-DR) survival signals in MM cells, and 
      P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) drug 
      transporter expression. Further, co-culture enhanced in vitro angiogenesis, MMP-2 
      activity, and protected MM cells from drug-induced decreases in viability. In 
      summary, we provide an underlying mechanism by which obesity can impair the drug 
      response to MM and allow for recurrence and/or disease progression.
FAU - Ochiai, Maria
AU  - Ochiai M
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - Fierstein, Sara
AU  - Fierstein S
AUID- ORCID: 0000-0002-3192-6530
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - XsSali, Farouq
AU  - XsSali F
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - DeVito, Nicholas
AU  - DeVito N
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - Purkey, Laura R
AU  - Purkey LR
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - May, Rebecca
AU  - May R
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - Correa-Medina, Abraham
AU  - Correa-Medina A
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - Kelley, Mary
AU  - Kelley M
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - Page, Thomas D
AU  - Page TD
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
FAU - DeCicco-Skinner, Kathleen
AU  - DeCicco-Skinner K
AUID- ORCID: 0000-0002-0256-5609
AD  - Department of Biology, American University, 4400 Massachusetts Ave, NW, 
      Washington, DC 20016, USA.
LA  - eng
PT  - Journal Article
DEP - 20230831
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10486466
OTO - NOTNLM
OT  - BMI
OT  - P-glycoprotein
OT  - adipocyte
OT  - multiple myeloma
OT  - obesity
OT  - resistance
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/09 11:46
MHDA- 2023/09/09 11:47
PMCR- 2023/08/31
CRDT- 2023/09/09 01:15
PHST- 2023/07/12 00:00 [received]
PHST- 2023/08/13 00:00 [revised]
PHST- 2023/08/24 00:00 [accepted]
PHST- 2023/09/09 11:47 [medline]
PHST- 2023/09/09 11:46 [pubmed]
PHST- 2023/09/09 01:15 [entrez]
PHST- 2023/08/31 00:00 [pmc-release]
AID - cancers15174347 [pii]
AID - cancers-15-04347 [pii]
AID - 10.3390/cancers15174347 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Aug 31;15(17):4347. doi: 10.3390/cancers15174347.