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), CD163Tim4 (P3), and CD163Tim4+. 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.