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

Autor: Evdokia Dimitriadis, Lois A. Salamonsen, Peter K. Nicholls, Tom Jobling, Joanne Yap
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Adult
STAT3 Transcription Factor
medicine.medical_specialty
Stromal cell
lcsh:QH471-489
Uterus
Suppressor of Cytokine Signaling Proteins
Endometrium
lcsh:Gynecology and obstetrics
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
Cell Line
Tumor
Carcinoma
Medicine
lcsh:Reproduction
Humans
Interleukin-11 Receptor alpha Subunit
Therapeutic Irrigation
lcsh:RG1-991
030304 developmental biology
Aged
Aged
80 and over
0303 health sciences
business.industry
Endometrial cancer
Research
Obstetrics and Gynecology
Cancer
Middle Aged
medicine.disease
Interleukin-11
Epithelium
3. Good health
Endometrial Neoplasms
Up-Regulation
medicine.anatomical_structure
Reproductive Medicine
Suppressor of Cytokine Signaling 3 Protein
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
business
Developmental Biology
Zdroj: Reproductive Biology and Endocrinology : RB&E
Reproductive Biology and Endocrinology, Vol 8, Iss 1, p 63 (2010)
ISSN: 1477-7827
Popis: 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.
Databáze: OpenAIRE
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