Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

Abstract

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

The complex role of IL-10 in malignant ascites: a review

“…Recent studies identified cancer stem cells as a possible source of IL-10. Gening et al found a strongly positive relationship between stem-like tumor cells (CD45-CD44+CD133-) and IL-10 levels in MA [ 64 ]. Raghavan et al established a hanging drop spheroid model and found that hetero-spheroids containing cancer stem cells and M2-macrophages (CSC/M2 hetero-spheroids) could secrete IL-10, indicating CSCs from MA can produce IL-10 under M2-macrophage interaction.…”

Friend and foe: the regulation network of ascites components in ovarian cancer progression

“…The upregulation of IL-10 in the ascites microenvironment is associated with increased production of ascites, poor prognosis, and ovarian cancer recurrence. The combination of IL-10 and IL-4 in ascites has the potential for accurately predicting the stage of ovarian tumors (Gening et al 2021). IL-10 affects ovarian cancer progression mainly by regulating antitumor immunity.…”

UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer

“…The presence of malignant ascites allows dissemination of EOC tumor cells as spheroids to other peritoneal and abdominal sites [ 8 ]. EOC spheroids harbor stem-like tumor-initiating cells (TICs) and present significant challenges to successful therapy of metastatic EOC as they promote chemoresistance and disease recurrence [ 9 – 11 ]. Furthermore, the complex and immunosuppressive tumor microenvironment (TME) of EOC presents significant challenges to treatment and promotes survival and metastasis of TICs [ 12 ].…”