Am J Cancer Res 2012;2(5):566-580
Original Article
Profiling of cytokines in human epithelial ovarian cancer ascites
Isabelle Matte, Denis Lane, Claude Laplante, Claudine Rancourt, Alain Piché
Département de Microbiologie et Infectiologie, Département de Pathologie, Faculté de Médecine, Université de Sherbrooke,
3001, 12ième Avenue Nord, Sherbrooke, Canada J1H 5N4
Received July 9, 2012; Accepted August 2, 2012; Epub August 20, 2012; Published September 15, 2012
Abstract: Background: The behavior of tumor cells is influenced by the composition of the surrounding tumor environment. The
importance of ascites in ovarian cancer (OC) progression is being increasingly recognized. The characterization of soluble
factors in ascites is essential to understand how this environment affects OC progression. The development of cytokine arrays
now allows simultaneous measurement of multiple cytokines per ascites using a single array. Methods: We applied a multiplex
cytokine array technology that simultaneously measures the level of 120 cytokines in ascites from 10 OC patients. The ascites
concentration of a subset (n = 5) of cytokines that was elevated based on the multiplex array was validated by commercially
available ELISA. The ascites level of these 5 cytokines was further evaluated by ELISA in a cohort of 38 patients. Kaplan-Meier
analysis was used to assess the association of cytokine expression with progression-free survival (PFS) in this cohort. Results:
We observed a wide variability of expression between different cytokines and levels of specific cytokines also varied in the 10
malignant ascites tested. Fifty-three (44%) cytokines were not detected in any of the 10 ascites. The level of several factors
including, among others, angiogenin, angiopoietin-2, GRO, ICAM-1, IL-6, IL-6R, IL-8, IL-10, leptin, MCP-1, MIF NAP-2,
osteprotegerin (OPG), RANTES, TIMP-2 and UPAR were elevated in most malignant ascites. Higher levels of OPG, IL-10 and
leptin in OC ascites were associated with shorter PFS. IL-10 was shown to promote the anti-apoptotic activity of malignant
ascites whereas OPG did not. Conclusion: Our data demonstrated that there is a complex network of cytokine expression in OC
ascites. Characterization of cytokine profiles in malignant ascites may provide information from which to prioritize key functional
cytokines and understand the mechanism by which they alter tumor cells behavior. A better understanding of the cytokine
network is essential to determine the role of ascites in OC progression. (AJCR0000136).
Keywords: Ascites, ovarian cancer, tumor environment, cytokines, mulitplex array, IL-10
Address all correspondence to:
Dr. Alain Piché
Département de Microbiologie et Infectiologie
Université de Sherbrooke, 3001
12ième Avenue Nord
Sherbrooke, Québec, Canada J1H 5N4.
Tel: (819) 564-5321; Fax: (819) 564-5392
E-mail: alain.piche@usherbrooke.ca
Original Article
Profiling of cytokines in human epithelial ovarian cancer ascites
Isabelle Matte, Denis Lane, Claude Laplante, Claudine Rancourt, Alain Piché
Département de Microbiologie et Infectiologie, Département de Pathologie, Faculté de Médecine, Université de Sherbrooke,
3001, 12ième Avenue Nord, Sherbrooke, Canada J1H 5N4
Received July 9, 2012; Accepted August 2, 2012; Epub August 20, 2012; Published September 15, 2012
Abstract: Background: The behavior of tumor cells is influenced by the composition of the surrounding tumor environment. The
importance of ascites in ovarian cancer (OC) progression is being increasingly recognized. The characterization of soluble
factors in ascites is essential to understand how this environment affects OC progression. The development of cytokine arrays
now allows simultaneous measurement of multiple cytokines per ascites using a single array. Methods: We applied a multiplex
cytokine array technology that simultaneously measures the level of 120 cytokines in ascites from 10 OC patients. The ascites
concentration of a subset (n = 5) of cytokines that was elevated based on the multiplex array was validated by commercially
available ELISA. The ascites level of these 5 cytokines was further evaluated by ELISA in a cohort of 38 patients. Kaplan-Meier
analysis was used to assess the association of cytokine expression with progression-free survival (PFS) in this cohort. Results:
We observed a wide variability of expression between different cytokines and levels of specific cytokines also varied in the 10
malignant ascites tested. Fifty-three (44%) cytokines were not detected in any of the 10 ascites. The level of several factors
including, among others, angiogenin, angiopoietin-2, GRO, ICAM-1, IL-6, IL-6R, IL-8, IL-10, leptin, MCP-1, MIF NAP-2,
osteprotegerin (OPG), RANTES, TIMP-2 and UPAR were elevated in most malignant ascites. Higher levels of OPG, IL-10 and
leptin in OC ascites were associated with shorter PFS. IL-10 was shown to promote the anti-apoptotic activity of malignant
ascites whereas OPG did not. Conclusion: Our data demonstrated that there is a complex network of cytokine expression in OC
ascites. Characterization of cytokine profiles in malignant ascites may provide information from which to prioritize key functional
cytokines and understand the mechanism by which they alter tumor cells behavior. A better understanding of the cytokine
network is essential to determine the role of ascites in OC progression. (AJCR0000136).
Keywords: Ascites, ovarian cancer, tumor environment, cytokines, mulitplex array, IL-10
Address all correspondence to:
Dr. Alain Piché
Département de Microbiologie et Infectiologie
Université de Sherbrooke, 3001
12ième Avenue Nord
Sherbrooke, Québec, Canada J1H 5N4.
Tel: (819) 564-5321; Fax: (819) 564-5392
E-mail: alain.piche@usherbrooke.ca
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American Journal of Cancer Research
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