Role of Adipose Cells in Tumor Microenvironment - The Mechanobiology of Obesity and Related Diseases - page 266

factors secreted by CAF [ 40 - 42 ]. While bone marrow-derived leukocytes func-
tionally contribute to the tumor microenvironment [ 43 , 44 ], MSC appear to be the
predominant progenitors of CAF [ 34 , 45 ], and recent data show that these MSC are
at least partly recruited from WAT [ 17 , 18 ]. In return, the tumor appears to
activate WAT-derived cells in a way that promotes their cancer-promoting effects
[ 46 , 47 ].
This chapter will cover the known and hypothetical links of adipose tissue to
cancer. The discussion will span from the role of adipokines in WAT and tumors
to advanced animal and ex vivo tissue culture models for studying tumorigenic
functions of adipose cells. Specifically, we will focus on the roles of cells derived
from WAT within tumor microenvironment. Key functions proposed for indi-
vidual cell populations of WAT are listed in Table 1 .
2 Functions of WAT-Derived Cells in Tumor
Microenvironment
2.1 Adipokines and Cancer
Adipokines are polypeptide hormones, cytokines, and other bioactive factors
secreted by WAT, the largest endocrine organ. Over the past decade, it has been
well appreciated that adipokines modulate events ranging from cell growth and
immune response to ECM remodeling, energy balance, and metabolism [ 6 ].
Currently, there are more than 50 different adipokines known [ 48 , 49 ], for some of
which cell types producing them are identified (Fig. 2 ). In obesity, with the
increase in adipose tissue mass and cell number, circulating adipokines levels are
altered. In addition to the effects of adipokine deregulation on systemic physiology
implicating on cancer, many appear to have direct effects on tumor cells [ 50 ].
Among described adipokines, leptin, adiponectin, interleukin-6 (IL-6) and insulin-
like growth factor 1 (IGF-1) have been most widely studied for their possible roles
in the progression of obesity-related cancers [ 9 , 10 , 29 , 51 ].
Many adipoknes are secreted by differentiated adipocytes. Leptin is an adipo-
cyte-secreted hormone that regulates energy intake and metabolism, mainly
through its receptor in the brain [ 52 ]. However, leptin receptor expression extends
to many cell types, including cancer cells. Being highly increased in the circulation
of obese individuals, leptin has been extensively investigated for its potential role
in the pathogenesis of cancer [ 53 ]. Leptin is a pleiotropic hormone being mito-
genic, antiapoptotic, proangiogenic, and proinflammatory in various cellular
systems [ 54 ]. Leptin stimulates cell growth, migration, and invasion in tumor
models, as well as angiogenesis, which all could be relevant in the pathogenesis of
cancer [ 55 , 56 ]. Leptin also increases the production of cancer-stimulating cyto-
kines by macrophages [ 57 ]. Adiponectin is another important adipocyte-derived