Biomedical Engineering Reference
In-Depth Information
cancer cells exhibit heightened incorporation of exogenous free palmitate into
glycerophospholipids, sphingolipids, and ether lipids compared to less aggressive
cancer cells, with increased generation of several tumor-promoting lipid signaling
molecules [
130
].
As lipid metabolism becomes a hallmark of cancer progression, understanding
the role of WAT has become critical. Adipocytes, storing large amounts of lipids
have been recently recognized as a potentially important fuel reservoir that tumors
may be able to hijack [
131
]. WAT surrounding tumors undergoes remodeling a
hallmark of which is lipid droplet loss by adipocytes [
112
]. This delipidation in
tumor-associated adipocytes possibly occurs to the tumor benefit [
29
]. It has been
proposed to be the manifestation of lipid exchange between WAT and tumor
[
132
]. On the other hand, studies in animal models have demonstrated the
recruitment of ASC from WAT to tumors, where they can differentiate into
intratumoral adipocytes [
33
]. Our data suggest that these de novo adipocytes
support malignant cell proliferation and survival, possibly as an energy source.
Intratumoral adipocytes also appear to engage in cancer progression and metastatic
dissemination [
133
,
134
]. However the function of intratumoral adipocytes is still
largely unknown, and it is unclear why they tend to be larger in tumors of obese
animals that grow faster [
33
].
2.6 Other Molecular Mechanisms Mediating Adipose
Cell-Driven Cancer Progression
It is not clear which molecular signaling cascades triggered by WAT-derived cells
are key in promoting tumor invasiveness and metastasis. Many molecules secreted
by adipocytes and ASC can exacerbate cancer cell aggressiveness through
increasing their migratory and invasive properties by modulating the ECM [
135
].
On the other hand, several adipokines have been shown to promote tumor pro-
gression through the induction of the EMT and increase in the generation of cancer
stem cells. It is known that the EMT process involves not only the induction of
increased tumor migration and invasion during the metastatic process, but also the
generation of cancer cells with stem cell-like characteristics that acquire resistance
to chemo- and radiotherapy. Like bone marrow MSC, ASC have been proposed to
promote tumor EMT through their direct action on malignant cells [
96
]. Inter-
estingly, in WAT-derived cancers called liposarcomas the aggressive malignant
population with ASC properties appears to serve as the cancer-initiating cells
[
136
]. In obesity, the ASC population is expanded, and therefore could potentially
become more bioavailable as a cancer-promoting entity for growing tumors.
WAT-derived cells could also mediate resistance to therapy and poorer outcomes.
In addition, the role of adipocytes in oxidative damage has been a subject of
investigation [
137
]. Reactive oxygen species (ROS), the ions formed by the
incomplete one-electron reduction of oxygen, are generated in mitochondria and
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