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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Hypoxia
  • Cell Movement* / drug effects
  • Cells, Cultured
  • Chemokine CXCL6 / genetics
  • Chemokine CXCL6 / metabolism
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Disease Progression
  • Down-Regulation
  • Endometriosis / enzymology*
  • Endometriosis / genetics
  • Endometriosis / pathology
  • Endometrium / drug effects
  • Endometrium / enzymology*
  • Endometrium / pathology
  • Female
  • Humans
  • Middle Aged
  • Prospective Studies
  • Stromal Cells / drug effects
  • Stromal Cells / enzymology*
  • Stromal Cells / pathology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult


  • CXCL6 protein, human
  • Chemokine CXCL6
  • Dipeptidyl-Peptidase IV Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4