Adipocytes contribute to the growth and progression of multiple myeloma: Unraveling obesity related differences in adipocyte signaling

被引：58

作者：

Bullwinkle, Erica M. ^{[1
]}

Parker, Melissa D. ^{[1
]}

Bonan, Nicole F. ^{[1
]}

Falkenberg, Lauren G. ^{[1
]}

Davison, Steven P. ^{[2
]}

DeCicco-Skinner, Kathleen L. ^{[1
]}

机构：

[1] Amer Univ, Dept Biol, 101 Hurst Hall,4400 Massachusetts Ave,NW, Washington, DC 20016 USA

[2] DaVinci Plast Surg, Washington, DC 20016 USA

来源：

CANCER LETTERS | 2016年 / 380卷 / 01期

关键词：

Multiple myeloma; Adipocyte; Obesity; Adhesion; Angiogenesis; Adipose-derived stem cells; MESENCHYMAL STEM-CELLS; BONE-MARROW ANGIOGENESIS; BODY-MASS INDEX; ADIPOSE-TISSUE; TUMOR MICROENVIRONMENT; CANCER; PROLIFERATION; INFLAMMATION; DIFFERENTIATION; METASTASIS;

D O I：

10.1016/j.canlet.2016.06.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：114 / 121

页数：8

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