Role of Adipose Cells in Tumor Microenvironment - The Mechanobiology of Obesity and Related Diseases - page 264

1 Introduction
1.1 Obesity and Tumor Microenvironment
Obesity, defined as the body mass index (BMI = weight/height 2 )ofC30 kg/m 2 ,is
a pathological condition responsible for the global health crisis affecting more than
10 % population worldwide [ 1 , 2 ]. Accumulating epidemiological evidences
demonstrate that obesity is associated with high risks of colorectal, breast, endo-
metrial, esophageal, kidney, thyroid, gallbladder and pancreatic cancer [ 3 ]. For
other cancer types association data are also emerging [ 4 , 5 ]. The percentage of
cancer cases attributed to obesity varies widely for different cancer types but is as
high as 40 % for some cancers, such as endometrial and esophageal adenocarci-
nomas. Importantly, obesity is also correlated with poor prognosis of many cancer
types, indicating its effect on disease progression [ 6 - 8 ]. The underlying molecular
mechanisms remain unclear [ 9 , 10 ]. Given the significant impact of obesity on
cancer mortality, increasing efforts have been devoted to research focusing on the
obesity-cancer link [ 11 ]. Tumor microenvironment is partly shaped as a result of
adjacent resident cell infiltration in response to factors released by hypoxic and
inflammatory factors [ 12 ]. In addition, recruitment of progenitor cells from remote
organs is also important in disease [ 13 ]. The implication of progenitor cells,
mobilized from distant organs, as building blocks for tumor vasculature and stroma
has been demonstrated in animal bone marrow transplantation models [ 14 - 16 ].
Recent studies have uncovered adipose tissue as alternative source of progenitor
cells recruited by tumors [ 17 , 18 ]. The studies discussed in this chapter overview
previously overseen roles of WAT-derived cells in tumor microenvironment.
1.2 Cells Composing Adipose Tissue
Obese people accumulate excessive body fat in white adipose tissue (WAT), a
loose connective tissue comprising depots distributed throughout the body [ 19 ].
The primary role of adipose tissue is the storage of triacylglycerides and main-
tenance of metabolic homeostasis [ 20 , 21 ]. In both subcutaneous and visceral
locations, this organ is composed of white adipocytes and the stromal vascular
fraction (SVF) cells [ 22 - 24 ]. White adipocytes contain a large lipid droplet sur-
rounded by a thin layer of cytoplasm. As shown in Fig. 1 , the SVF is a mixture of
cell populations including incompletely differentiated preadipocytes, heteroge-
neous adipose stromal cells (ASC), endothelial cells from various vessel types and
a diversity of leukocytes, such as macrophages/other monocytes and lymphocytes
[ 24 ]. ASC are the mesenchymal stem/stromal cells (MSC) of WAT [ 13 , 22 , 25 ].
WAT expansion relies not only on adipocyte hypertrophy but also on proliferation
of ASC that, upon differentiation, generate new adipocytes [ 2 , 26 , 27 ]. Recent