CD26/DPPIV down-regulation in endometrial stromal cell migration in endometriosis

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• 作者：Chin Wen Tan ; B.Eng.^a ; ^b ; Yie Hou Lee ; Ph.D.^a ; Heng Hao Tan ; M.B. ; B.S.^c ; Matthew Sie Kuei Lau ; M.B. ; B.S.^c ; Mahesh Choolani ; M.B. ; B.S. ; Ph.D.^b ; Linda Griffith ; Ph.D.^a ; ^d ; ^e ; Jerry Kok Yen Chan ; M.B. ; Ph.D.^a ; ^b ; ^c ; ^f ; ^{jerrychan@nus.edu.sg" class="auth_mail}
• 关键词：Endometriosis ; CD26/DPPIV ; endometrial stromal cells ; migration ; hypoxia
• 刊名：Fertility and Sterility
• 出版年：July 2014
• 年：2014
• 卷：102
• 期：1
• 页码：167-177.e9
• 全文大小：1973 K

文摘

To test the hypothesis that endometrial stromal cells (ESCs) in endometriosis exhibit increased cell motility under hypoxia.

Design

Prospective case-control study.

Setting

University research laboratory.

Patient(s)

Women with endometriosis (n = 18) or benign gynecological disease (n = 19).

Intervention(s)

Eutopic ESCs were cultured under normoxia (20% O₂) or hypoxia (6.5% O₂), and migration and invasion capacity assayed, with pathway-focused polymerase chain reaction (PCR) array and ELISAs performed. CD26/dipeptidyl peptidase IV (DPPIV) expression was determined by flow cytometric analysis and enzymatic activity assay. The ESCs supplemented with Diprotin A (CD26 inhibitor), stromal cell-derived factor-1伪, or AMD3100 (C-X-C motif receptor 4; CXCR4 blocker) were assayed for their migratory potential.

Main Outcome Measure(s)

Endometrial stromal cell migration and invasion under hypoxia.

Result(s)

Endometriotic ESCs showed significantly higher migration and invasion through collagen gels under hypoxia compared with nonendometriotic ESCs. The PCR array revealed down-regulation of the migration inhibitor CD26/DPPIV and up-regulation of angiogenic factors (vascular endothelial growth factor A, C-X-C motif Ligand 6; CXCL6) in endometriotic ESCs under hypoxia. The CD26/DPPIV surface expression and activity as well as angiogenic protein secretions suggested that the molecular mechanisms underlying aberrant migratory and angiogenic behavior in endometriotic ESCs. A combinatorial treatment with diprotin A and stromal cell-derived factor-1伪 effectively enhanced migration and invasion preferentially in endometriotic ESCs cultured hypoxically.

Conclusion(s)

Loss of CD26/DPPIV under hypoxia and the subsequent increase in migratory and angiogenic factors may favor conditions for lesion development in endometriosis.