Adipocytes contribute to the growth and progression of multiple myeloma: Unraveling obesity related differences in adipocyte signaling.
The prevalence of obesity over the last several decades in the United States has tripled among children and doubled among adults. Obesity increases the incidence and progression of multiple myeloma (MM), yet the molecular mechanisms by which adipocytes contribute to cancer development and patient prognosis have yet to be fully elucidated. Here, we obtained human adipose-derived stem cells (ASCs) from twenty-nine normal (BMI = 20-25 kg/m(2)), overweight (25-30 kg/m(2)), obese (30-35 kg/m(2)), or super obese (35-40 kg/m(2)) patients undergoing elective liposuction. Upon differentiation, adipocytes were co-cultured with RPMI-8226 and NCI-H929 MM cell lines. Adipocytes from overweight, obese and super obese patients displayed increased PPAR-gamma, cytochrome C, interleukin-6, and leptin protein levels, and decreased fatty acid synthase protein. 8226 MM cells proliferated faster and displayed increased pSTAT-3/STAT-3 signaling when cultured in adipocyte conditioned media. Further, adipocyte conditioned media from obese and super obese patients significantly increased MM cell adhesion, and conditioned media from overweight, obese and super obese patients enhanced tube formation and expression of matrix metalloproteinase-2. In summary, our data suggest that adipocytes in the MM microenvironment contribute to MM growth and progression and should be further evaluated as a possible therapeutic target.
Department of Biology, American University, Washington, DC 20016, USA.
Erica M
EM
Bullwinkle
Department of Biology, American University, Washington, DC 20016, USA.
Melissa D
MD
Parker
Department of Biology, American University, Washington, DC 20016, USA.
Nicole F
NF
Bonan
Department of Biology, American University, Washington, DC 20016, USA.
Lauren G
LG
Falkenberg
DaVinci Plastic Surgery, Washington, DC 20016, USA.
Steven P
SP
Davison
Department of Biology, American University, Washington, DC 20016, USA. Electronic address: decicco@american.edu.
Kathleen L
KL
DeCicco-Skinner
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D018450:Disease Progression; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009101:Multiple Myeloma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D019899:Paracrine Communication; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment
D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D020738:Leptin; D047495:PPAR gamma; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D045304:Cytochromes c; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Adhesion; Adipocyte; Adipose-derived stem cells; Angiogenesis; Multiple myeloma; Obesity