Dissimilar tumor cell populations in ascitic fluid of ovarian cancer patients

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.

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High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer [see comments]

Blood ◽

10.1182/blood.v81.2.424.424 ◽

1993 ◽

Vol 81 (2) ◽

pp. 424-429 ◽

Cited By ~ 33

Author(s):

DP Barton ◽

DK Blanchard ◽

B Michelini-Norris ◽

SV Nicosia ◽

D Cavanagh ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid ◽

Total Protein ◽

Interleukin 2 ◽

Serum Levels ◽

Ca 125 ◽

Soluble Interleukin 2 Receptor ◽

Advanced Epithelial Ovarian Cancer

Abstract This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.

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41P Stem-like tumour cell populations and cytokine profile of the ascitic fluid in ovarian cancer

Annals of Oncology ◽

10.1016/j.annonc.2020.08.2200 ◽

2020 ◽

Vol 31 ◽

pp. S1229-S1230

Author(s):

S. Gening ◽

I. Antoneeva ◽

T. Abakumova ◽

A. Rizvanov ◽

D. Gafurbaeva ◽

...

Keyword(s):

Ovarian Cancer ◽

Ascitic Fluid ◽

Tumour Cell ◽

Cytokine Profile ◽

Cell Populations

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Biomarker potential of IL-6 and VEGF-A in ascitic fluid of epithelial ovarian cancer patients

Clinica Chimica Acta ◽

10.1016/j.cca.2018.03.019 ◽

2018 ◽

Vol 482 ◽

pp. 27-32 ◽

Cited By ~ 12

Author(s):

Venus Dalal ◽

Raman Kumar ◽

Sunesh Kumar ◽

Alpana Sharma ◽

Lalit Kumar ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid

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Tumor cell-specificBRCA1andRASSF1Ahypermethylation in serum, plasma and peritoneal fluid from ovarian cancer patients

The Women s Oncology Review ◽

10.3109/14733400500093346 ◽

2005 ◽

Vol 5 (1) ◽

pp. 19-21

Author(s):

Antonia Anna Anzalone ◽

Lucia Lettini ◽

Ester Fonsatti ◽

Michele Maio

Keyword(s):

Ovarian Cancer ◽

Tumor Cell ◽

Cancer Patients ◽

Peritoneal Fluid

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Affinity chromatography separation of tumor associated antigens from ascitic fluid of ovarian cancer patients

Gynecologic Oncology ◽

10.1016/0090-8258(83)90062-8 ◽

1983 ◽

Vol 15 (3) ◽

pp. 428-433 ◽

Cited By ~ 2

Author(s):

R. Hill ◽

B. Daunter ◽

P.A. Silburn ◽

S.K. Khoo ◽

E.V. Mackay

Keyword(s):

Ovarian Cancer ◽

Affinity Chromatography ◽

Cancer Patients ◽

Ascitic Fluid ◽

Tumor Associated Antigens

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Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients

BMC Cancer ◽

10.1186/1471-2407-5-133 ◽

2005 ◽

Vol 5 (1) ◽

Cited By ~ 47

Author(s):

Beate Gericke ◽

Jens Raila ◽

Jalid Sehouli ◽

Sophie Haebel ◽

Dominique Könsgen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid

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Neutralisation of adenovirus infectivity by ascitic fluid from ovarian cancer patients

Gene Therapy ◽

10.1038/sj.gt.3301152 ◽

2000 ◽

Vol 7 (8) ◽

pp. 637-643 ◽

Cited By ~ 49

Author(s):

Y Stallwood ◽

K D Fisher ◽

P H Gallimore ◽

V Mautner

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Ascitic Fluid

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Sensitivity of EGFR/HER-2 Positive Cells Isolated from Ascitic Fluid of Advanced Ovarian Cancer Patients to EGFR/HER-2 Inhibitors

Applied Sciences ◽

10.3390/app10072343 ◽

2020 ◽

Vol 10 (7) ◽

pp. 2343

Author(s):

Kenny Chitcholtan ◽

Dianne Harker ◽

Bryony Simcock ◽

Peter Sykes

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Ascitic Fluid ◽

Cancer Cell ◽

Protein Level ◽

Advanced Ovarian Cancer ◽

Immunofluorescent Staining ◽

Ovarian Cancer Cells ◽

Her 2

Background: advanced ovarian cancer often presents with ascites. These ascites contain small clusters of cancer cells, which may contribute greatly to the metastatic potential of ovarian cancer in the peritoneal cavity. Therefore, understanding the unique protein expressions of this cell population will provide vital information for the development of tailored, targeted treatment. In this study, we isolate floating ovarian cancer cells from ovarian cancer patient ascitic fluid and use these cells to document that the expression of EGFR/HER-2 proteins may be essential for the growth and survival of these floating cancer cell clusters. Methods: ascitic fluid-derived cells were isolated from ascitic fluid by using Ficoll separation. Cells were cultured in a non-adherent condition for six days. The protein level of EGFR, HER-2, AKT, and ERK and their phosphorylation in ovarian cancer cell lines were determined by immunofluorescence. The immunofluorescent staining for proteins presented in ascitic fluid-derived cells determined the intensity profile of each protein using Carl Zeiss Blue software. Results: Isolated ovarian cancer cells from ascitic fluid have a measurable level of EGFR and HER-2 proteins. The inhibition of EGFR and EGFR/HER-2 positive cells with gefitinib and canertinib selectively disrupts cell viability and the protein level of EGFR, HER-2, AKT and ERK and their respective phosphorylation status. In addition, the dual EGFR/HER-2 inhibitor canertinib demonstrates greater anti-tumour effects than gefitinib in EGFR/HER-2 positive cells. Conclusion: These studies reveal an important role of multiple activation of receptor tyrosine kinases in floating ovarian cancer cells, as well as the importance of a dual EGFR/HER-2 inhibitor used as alternative adjuvant therapy in advanced ovarian cancer patients.

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