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Fertil Steril. 2014 Jul;102(1):167-177.e9. doi: 10.1016/j.fertnstert.2014.04.001. Epub 2014 May 10.

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

Author information

1
BioSystems and Micromechanics, Singapore-MIT Alliance for Research & Technology, Singapore; Department of Obstetrics and Gynaecology, National University of Singapore, Singapore.
2
BioSystems and Micromechanics, Singapore-MIT Alliance for Research & Technology, Singapore.
3
Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore.
4
Department of Obstetrics and Gynaecology, National University of Singapore, Singapore.
5
BioSystems and Micromechanics, Singapore-MIT Alliance for Research & Technology, Singapore; Department of Biological and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Center for Gynepathology Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
6
BioSystems and Micromechanics, Singapore-MIT Alliance for Research & Technology, Singapore; Department of Obstetrics and Gynaecology, National University of Singapore, Singapore; Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore; Cancer & Stem Cell Biology Program, Duke NUS Graduate Medical School, Singapore. Electronic address: jerrychan@nus.edu.sg.

Abstract

OBJECTIVE:

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-1α, 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-1α 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.

KEYWORDS:

CD26/DPPIV; Endometriosis; endometrial stromal cells; hypoxia; migration

[Indexed for MEDLINE]

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