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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma

Authors: Joanne Yap, Lois A Salamonsen, Tom Jobling, Peter K Nicholls, Evdokia Dimitriadis

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

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Abstract

Background

Interleukin (IL) 11 is produced by human endometrium and endometrial cancer tissue. It has roles in endometrial epithelial cell adhesion and trophoblast cell invasion, two important processes in cancer progression. This study aimed to determine the levels of IL11 in uterine lavage fluid in women with endometrial cancer and postmenopausal women. It further aimed to determine the levels of IL11 protein and its signaling molecules in human endometrial cancer of varying grades, and endometrium from postmenopausal women and IL11 signalling mechanisms in endometrial cancer cell lines.

Methods

IL11 levels in uterine lavage were measured by ELISA. IL11, IL11 receptor(R) α, phosphorylated (p) STAT3 and SOCS3 were examined by immunohistochemistry in endometrial carcinomas and in control endometrium from postmenopausal women and normal cycling women. The effect of IL11 on pSTAT3/STAT3 and SOCS3 protein abundance in endometrial cancer cell lines and non-cancer endometrial epithelial cells was determined by Western blot.

Results

IL11 was present in uterine flushings and was significantly higher in women with Grade 1 carcinomas compared to postmenopausal women (p < 0.05). IL11 immunostaining was significantly elevated in the endometrial tumour epithelial cells from Grade 1 and 3 compared to endometrial epithelium from postmenopausal and cycling women. IL11Rα immunostaining intensity was increased in cancer epithelium in the Grades 1 and 2 tumours compared to epithelium from postmenopausal women. Both IL11 and IL11Rα localized to vascular endothelial and smooth muscle cells while IL11 also localized to subsets of leucocytes in the cancer tissues. pSTAT3 was found in both the tumour epithelial and stromal compartments but was maximal in the tumour epithelial cells, while SOCS3 was predominantly found in the tumour epithelial cells. pSTAT3 staining intensity was significantly higher in Grade 1 and 2 tumour epithelial cells compared to epithelial cells from cycling and postmenopausal women. SOCS3 staining intensity did not differ between between each tumour and postmenopausal endometrial epithelium but SOCS3 in cycling endometrium was significantly higher compared to postmonopausal and Tumour Grades 2 and 3. IL11 increased pSTAT3/STAT3 in all tumour cell lines, while SOCS3 abundance was increased only in one tumour cell line.

Conclusions

The present study suggests that IL11 in uterine washings may be useful as a diagnostic marker for early stage endometrial cancer. It indicates that IL11, along with its specific receptor, IL11Rα, and downstream signalling molecules, STAT3 and SOCS3, are likely to play a role in the progression of endometrial carcinoma. The precise role of IL11 in endometrial cancer remains to be elucidated.
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Literature
1.
Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics, 1999. CA Cancer J Clin. 1999, 49 (1): 8-31. 10.3322/canjclin.49.1.8. 31CrossRefPubMed
2.
3.
4.
Somoye G, Olaitan A, Mocroft A, Jacobs I: Age related trends in the incidence of endometrial cancer in South East England 1962-1997. J Obstet Gynaecol. 2005, 25 (1): 35-38. 10.1080/01443610400024690.CrossRefPubMed
5.
Du X, Williams DA: Interleukin-11: review of molecular, cell biology, and clinical use. Blood. 1997, 89 (11): 3897-3908.PubMed
6.
Darnell JE: STATs and gene regulation. Science. 1997, 277 (5332): 1630-1635. 10.1126/science.277.5332.1630.CrossRefPubMed
7.
Wormald S, Hilton DJ: Inhibitors of cytokine signal transduction. J Biol Chem. 2004, 279 (2): 821-824. 10.1074/jbc.R300030200.CrossRefPubMed
8.
Greenhalgh CJ, Miller ME, Hilton DJ, Lund PK: Suppressors of cytokine signaling: Relevance to gastrointestinal function and disease. Gastroenterology. 2002, 123 (6): 2064-2081. 10.1053/gast.2002.37068.CrossRefPubMed
9.
Dimitriadis E, Stoikos C, Tan YL, Salamonsen LA: Interleukin 11 signaling components signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) regulate human endometrial stromal cell differentiation. Endocrinology. 2006, 147 (8): 3809-3817. 10.1210/en.2006-0264.CrossRefPubMed
10.
Marwood M, Visser K, Salamonsen LA, Dimitriadis E: Interleukin-11 and leukemia inhibitory factor regulate the adhesion of endometrial epithelial cells: implications in fertility regulation. Endocrinology. 2009, 150 (6): 2915-2923. 10.1210/en.2008-1538.CrossRefPubMed
11.
White CA, Zhang JG, Salamonsen LA, Baca M, Fairlie WD, Metcalf D, Nicola NA, Robb L, Dimitriadis E: Blocking LIF action in the uterus by using a PEGylated antagonist prevents implantation: a nonhormonal contraceptive strategy. Proc Natl Acad Sci USA. 2007, 104 (49): 19357-19362. 10.1073/pnas.0710110104.PubMedCentralCrossRefPubMed
12.
Dimitriadis E, Salamonsen LA, Robb L: Expression of interleukin-11 during the human menstrual cycle: coincidence with stromal cell decidualization and relationship to leukaemia inhibitory factor and prolactin. Mol Hum Reprod. 2000, 6 (10): 907-914. 10.1093/molehr/6.10.907.CrossRefPubMed
13.
Sales K, Grant V, Cook I, Maldonado-Perez D, Anderson R, Williams A, Jabbour H: Interleukin-11 in endometrial adenocarcinoma is regulated by prostaglandin F2alpha-F-prostanoid receptor interaction via the calcium-calcineurin-nuclear factor of activiated T cells pathway and negatively regulated by the regulator of calcineurin-1. American Journal of Pathology. 2010, 176 (1): 435-445. 10.2353/ajpath.2010.090403.PubMedCentralCrossRefPubMed
14.
Howlett M, Giraud AS, Lescesen H, Jackson CB, Kalantzis A, Van Driel IR, Robb L, Vander Hoek M, Ernst M, Minamoto T: The interleukin-6 family cytokine interleukin-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development. Gastroenterology. 2009, 136 (3): 967-977. 10.1053/j.gastro.2008.12.003.CrossRefPubMed
15.
Howlett M, Judd LM, Jenkins B, La Gruta NL, Grail D, Ernst M, Giraud AS: Differential regulation of gastric tumor growth by cytokines that signal exclusively through the coreceptor gp130. Gastroenterology. 2005, 129 (3): 1005-1018. 10.1053/j.gastro.2005.06.068.CrossRefPubMed
16.
Lewis VO, Ozawa MG, Deavers MT, Wang G, Shintani T, Arap W, Pasqualini R: The interleukin-11 receptor alpha as a candidate ligand-directed target in osteosarcoma: consistent data from cell lines, orthotopic models, and human tumor samples. Cancer Res. 2009, 69 (5): 1995-1999. 10.1158/0008-5472.CAN-08-4845.CrossRefPubMed
17.
Zurita AJ, Troncoso P, Cardo-Vila M, Logothetis CJ, Pasqualini R, Arap W: Combinatorial screenings in patients: the interleukin-11 receptor alpha as a candidate target in the progression of human prostate cancer. Cancer Res. 2004, 64 (2): 435-439. 10.1158/0008-5472.CAN-03-2675.CrossRefPubMed
18.
Devarajan E, Huang S: STAT3 as a central regulator of tumor metastases. Curr Mol Med. 2009, 9 (5): 626-633. 10.2174/156652409788488720.CrossRefPubMed
19.
Souckova K, Kovarik A, Dusek L, Humpolikova-Adamkova L, Lauerova L, Krejci E, Matouskova E, Bursikova E, Fojtova M, Kovarik J: Reduced inducibility of SOCS3 by interferon gamma associates with higher resistance of human breast cancer lines as compared to normal mammary epithelial cells. Neoplasma. 2009, 56 (5): 379-386. 10.4149/neo_2009_05_379.CrossRefPubMed
20.
Ruoslahti E, Yamaguchi Y: Proteoglycans as modulators of growth factor activities. Cell. 1991, 64 (5): 867-869. 10.1016/0092-8674(91)90308-L.CrossRefPubMed
21.
Paiva P, Salamonsen LA, Manuelpillai U, Dimitriadis E: Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation. Biol Reprod. 2009, 80 (2): 302-310. 10.1095/biolreprod.108.071415.PubMedCentralCrossRefPubMed
22.
Paiva P, Salamonsen LA, Manuelpillai U, Walker C, Tapia A, Wallace EM, Dimitriadis E: Interleukin-11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation. Endocrinology. 2007, 148 (11): 5566-5572. 10.1210/en.2007-0517.CrossRefPubMed
23.
Lopata A, Agresta F, Quinn M, Smith C, Ostor A, Salamonsen L: Detection of endometrial cancer by determination of matrix metalloproteinases in the uterine cavity. Gynecol Oncol. 2003, 90 (2): 318-324. 10.1016/S0090-8258(03)00328-7.CrossRefPubMed
24.
Hannan NJ, Stoikos CJ, Stephens AN, Salamonsen LA: Depletion of high-abundance serum proteins from human uterine lavages enhances detection of lower-abundance proteins. J Proteome Res. 2009, 8 (2): 1099-1103. 10.1021/pr800811y.CrossRefPubMed
25.
Dimitriadis E, Robb L, Salamonsen LA: Interleukin 11 advances progesterone-induced decidualization of human endometrial stromal cells. Mol Hum Reprod. 2002, 8 (7): 636-643. 10.1093/molehr/8.7.636.CrossRefPubMed
26.
Desai NN, Kennard EA, Kniss DA, Friedman CI: Novel human endometrial cell line promotes blastocyst development. Fertil Steril. 1994, 61 (4): 760-766.PubMed
27.
Menkhorst E, Salamonsen L, Robb L, Dimitriadis E: IL11 antagonist inhibits uterine stromal differentiation, causing pregnancy failure in mice. Biol Reprod. 2009, 80 (5): 920-927. 10.1095/biolreprod.108.073601.PubMedCentralCrossRefPubMed
28.
Cork BA, Tuckerman EM, Li TC, Laird SM: Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human endometrial cells in vitro. Mol Hum Reprod. 2002, 8 (9): 841-848. 10.1093/molehr/8.9.841.CrossRefPubMed
29.
Tsutsui S, Yasuda K, Suzuki K, Tahara K, Higashi H, Era S: Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep. 2005, 14 (2): 425-431.PubMed
30.
Soeda S, Nakamura N, Ozeki T, Nishiyama H, Hojo H, Yamada H, Abe M, Sato A: Tumor-associated macrophages correlate with vascular space invasion and myometrial invasion in endometrial carcinoma. Gynecol Oncol. 2008, 109 (1): 122-128. 10.1016/j.ygyno.2007.12.033.CrossRefPubMed
31.
Hanavadi S, Martin TA, Watkins G, Mansel RE, Jiang WG: Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer. Ann Surg Oncol. 2006, 13 (6): 802-808. 10.1245/ASO.2006.05.028.CrossRefPubMed
32.
Yamazumi K, Nakayama T, Kusaba T, Wen CY, Yoshizaki A, Yakata Y, Nagayasu T, Sekine I: Expression of interleukin-11 and interleukin-11 receptor alpha in human colorectal adenocarcinoma; immunohistochemical analyses and correlation with clinicopathological factors. World J Gastroenterol. 2006, 12 (2): 317-321.PubMedCentralPubMed
33.
White CA, Robb L, Salamonsen LA: Uterine extracellular matrix components are altered during defective decidualization in interleukin-11 receptor alpha deficient mice. Reprod Biol Endocrinol. 2004, 2: 76-10.1186/1477-7827-2-76.PubMedCentralCrossRefPubMed
34.
Nakayama T, Yoshizaki A, Izumida S, Suehiro T, Miura S, Uemura T, Yakata Y, Shichijo K, Yamashita S, Sekin I: Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells. Int J Oncol. 2007, 30 (4): 825-833.PubMed
35.
Yoshizaki A, Nakayama T, Yamazumi K, Yakata Y, Taba M, Sekine I: Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells. Int J Oncol. 2006, 29 (4): 869-876.PubMed
36.
Kilarski WW, Bikfalvi A: Recent developments in tumor angiogenesis. Curr Pharm Biotechnol. 2007, 8 (1): 3-9. 10.2174/138920107779941444.CrossRefPubMed
37.
Wen CY, Ito M, Matsuu M, Fukuda E, Shichijo K, Nakashima M, Nakayama T, Sekine I: Mechanism of the antiulcerogenic effect of IL-11 on acetic acid-induced gastric ulcer in rats. Life Sci. 2002, 70 (25): 2997-3005. 10.1016/S0024-3205(02)01552-7.CrossRefPubMed
38.
Dimitriadis E, Stoikos C, Baca M, Fairlie WD, McCoubrie JE, Salamonsen LA: Relaxin and prostaglandin E(2) regulate interleukin 11 during human endometrial stromal cell decidualization. J Clin Endocrinol Metab. 2005, 90 (6): 3458-3465. 10.1210/jc.2004-1014.CrossRefPubMed
39.
Lee TL, Yeh J, Van Waes C, Chen Z: Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas. Mol Cancer Ther. 2006, 5 (1): 8-19. 10.1158/1535-7163.MCT-05-0069.CrossRefPubMed
40.
Weber A, Hengge UR, Bardenheuer W, Tischoff I, Sommerer F, Markwarth A, Dietz A, Wittekind C, Tannapfel A: SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. Oncogene. 2005, 24 (44): 6699-6708. 10.1038/sj.onc.1208818.CrossRefPubMed
41.
Oshimo Y, Kuraoka K, Nakayama H, Kitadai Y, Yoshida K, Chayama K, Yasui W: Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma. Int J Cancer. 2004, 112 (6): 1003-1009. 10.1002/ijc.20521.CrossRefPubMed
42.
Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, Cervantes F, Barrios M, Colomer D, Heiniger A, Torres A: The suppressor of cytokine signaling-1 is constitutively expressed in chronic myeloid leukemia and correlates with poor cytogenetic response to interferon-alpha. Haematologica. 2004, 89 (1): 42-48.PubMed
43.
Li Z, Metze D, Nashan D, Muller-Tidow C, Serve HL, Poremba C, Luger TA, Bohm M: Expression of SOCS-1, suppressor of cytokine signalling-1, in human melanoma. J Invest Dermatol. 2004, 123 (4): 737-745. 10.1111/j.0022-202X.2004.23408.x.CrossRefPubMed
44.
Bellezza I, Neuwirt H, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A: Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer. Am J Pathol. 2006, 169 (6): 2199-2208. 10.2353/ajpath.2006.060171.PubMedCentralCrossRefPubMed
45.
Neuwirt H, Puhr M, Cavarretta IT, Mitterberger M, Hobisch A, Culig Z: Suppressor of cytokine signalling-3 is up-regulated by androgen in prostate cancer cell lines and inhibits androgen-mediated proliferation and secretion. Endocr Relat Cancer. 2007, 14 (4): 1007-1019. 10.1677/ERC-07-0172.CrossRefPubMed
Metadata
Title
Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma
Authors
Joanne Yap
Lois A Salamonsen
Tom Jobling
Peter K Nicholls
Evdokia Dimitriadis
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-63

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