Chin Wen Tan1, Yie Hou Lee2, Heng Hao Tan3, Matthew Sie Kuei Lau3, Mahesh Choolani4, Linda Griffith5, Jerry Kok Yen Chan6. 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.
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.
Authors: Anderson B Guimaraes-Costa; John P Shannon; Ingrid Waclawiak; Jullyanna Oliveira; Claudio Meneses; Waldione de Castro; Xi Wen; Joseph Brzostowski; Tiago D Serafim; John F Andersen; Heather D Hickman; Shaden Kamhawi; Jesus G Valenzuela; Fabiano Oliveira Journal: Nat Commun Date: 2021-05-28 Impact factor: 14.919
Authors: Jeannette Rudzitis-Auth; Sarah I Huwer; Claudia Scheuer; Michael D Menger; Matthias W Laschke Journal: Sci Rep Date: 2022-04-04 Impact factor: 4.996