Table 1. Examples of adipocyte-associated factors
2.2 Cancer-associated Macrophages
deprived from the omentum
In recent years, increasing attention has been focused on
cancer-associated macrophages (CAMs). Macrophages have a variety of
effects on the basis of their extreme plasticity in response to their
microenvironment[53]. In many previous studies,
most foci are gathered in macrophages isolated from peritoneal ascites
because they are abundant in thoracic and ascites of ovarian cancer
patients. Relevant results have demonstrated that ascites-deprived
macrophages express M1 and M2 polarization markers, which is named mixed
polarization[54]. In this review, we will discuss
reciprocity between ovarian cancer cells and macrophages deprived from
omentum adipose tissue. Unfortunately, relevant studies are limited.
Thus, whether previous results about the roles of macrophages stemming
from peritoneal ascites apply to macrophages originating from omentum
adipose tissue should be further verified.
Peritoneal injection into mice of the immortalized mouse ovarian
epithelial cell line ID8, which is labeled with Qdots (Qtracker705),
demonstrated that the area of aggregated omental macrophages attracts
more ovarian cancer cells. Further single-cell RNA sequencing analysis
of these macrophages indicated that common coexpressing macrophage
markers are Lyve-1, Cd163, and Tim4. Only CD169himacrophages expressed Lyve-1 at the same time, and only
CD169hi Lyve-1+ cells expressed
Cd163 and Tim4. According to their different expression status, the
authors divided four subtypes: CD163+Tim4+ (P1), CD163+Tim4− (P2), CD163−Tim4− (P3), and CD163−Tim4+. The significant feature of P1 macrophages,
which are distinguished from other subtypes, is they might originate
from embryos rather than monocytes, which is why they cannot be replaced
easily by other cell types. The specific deletion of P1 macrophages
would inhibit ovarian cancer cell metastasis, and their existence would
be the basis of the acquisition of invasive behavior of ovarian cancer
cells[55].
In addition, chemokines and their receptors form an important bridge
between macrophages and cancer cells. For example, in mouse models, the
expression of the chemokine ligand CCL6 presents significant changes in
omental macrophages while ovarian cancer cells colonize the omentum.
Similarly, CCL23, the human homolog of CCL6, was discovered in human
omental macrophages. CCR1, which is highly expressed in ovarian cancer
cells, can mediate ovarian cancer cell-enhanced migration and
metastasis[56]. Some blockers targeting at CCR1 or
CCL23 might improve the clinical outcome of ovarian cancer patients.
2.3 Cancer-associated mesenchymal stem cells deprived of omentum
In recent years, mesenchymal stem cells (MSCs) have attracted attention
because of their therapeutic potential in cancer. Huijuan Tang et al.
found that MSCs deprived of omentum adipose tissue tend to express more
carcinoma-associated-fibroblast markers through the TGF-β pathway to
support ovarian cancer cell growth and omental metastasis. Inhibition of
this differentiation would be a new therapeutic
target[57]. Coculturing ovarian cancer cell lines
and adipose-derived mesenchymal stem cells (ADSCs) in vitro and
in mouse xenograft models reached the same conclusion: adipose-derived
mesenchymal stem cells could promote ovarian cancer cell growth and
migration, and this process was inhibited by downregulating the
expression of MMP[58]. Other phenotype validation
experiments illustrated that MSCs deprived of omentum adipose tissue
would advance invasion and chemoresistance[59].
There is another perspective that ADSC-deprived exosomes could induce
the apoptosis of ovarian cancer cells, and the sequencing results showed
a great deal of miRNAs associated with ovarian cancer
survival[60]. Each conclusion provides an
important disease treatment idea for ovarian cancer.