PURPOSE: To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo. PATIENTS AND METHODS: IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied. RESULTS: IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR = 313 +/- 55 vs. 53 +/- 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01-21.23 pg/ml; mean 3.1 pg/ml) and benign disease patients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro. CONCLUSIONS: IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USPC.
PURPOSE: To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo. PATIENTS AND METHODS: IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied. RESULTS:IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR = 313 +/- 55 vs. 53 +/- 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01-21.23 pg/ml; mean 3.1 pg/ml) and benign diseasepatients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro. CONCLUSIONS:IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USPC.
Authors: Elizabeth L Kacel; Janae L Kirsch; Timothy S Sannes; Seema Patidar; Rachel Postupack; Sally Jensen; Shan Wong; Stephanie Garey; Stacy Dodd; Chantel M Ulfig; Christina S McCrae; Michael E Robinson; Jacqueline Castagno; Gregory S Schultz; Deidre B Pereira Journal: Health Psychol Date: 2019-08-01 Impact factor: 4.267
Authors: Dana M Roque; Stefania Bellone; Diana P English; Natalia Buza; Emiliano Cocco; Sara Gasparrini; Ileana Bortolomai; Elena Ratner; Dan-Arin Silasi; Masoud Azodi; Thomas J Rutherford; Peter E Schwartz; Alessandro D Santin Journal: Cancer Date: 2013-04-12 Impact factor: 6.860
Authors: Deidre B Pereira; Timothy Sannes; Stacy M Dodd; Sally E Jensen; Linda S Morgan; Edward K L Chan Journal: Brain Behav Immun Date: 2009-08-27 Impact factor: 7.217
Authors: E Cocco; S Bellone; K El-Sahwi; M Cargnelutti; F Casagrande; N Buza; F A Tavassoli; E R Siegel; I Visintin; E Ratner; D-A Silasi; M Azodi; P E Schwartz; T J Rutherford; S Pecorelli; A D Santin Journal: Br J Cancer Date: 2009-06-16 Impact factor: 7.640