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Reduced α-2,6 sialylation regulates cell migration in endometriosis.
Hum Reprod. 2019 03 01; 34(3):479-490.HR

Abstract

STUDY QUESTION

Is endometriosis associated with aberrant sialylation patterns and what is the potential impact of such anomalies on cell migratory properties?

SUMMARY ANSWER

The reduced α-2,6 sialylation patterns in the peritoneal fluid of endometriosis-affected women and in stromal and epithelial cells from endometriotic lesions could be associated with enhanced cell migration.

WHAT IS KNOWN ALREADY

Endometriosis is considered to be a benign disease although, like cancer, it has the characteristic of being an invasive disease with cells that have an enhanced capacity to migrate. Aberrant sialylation has been reported in various malignancies and it has been linked to tumour invasion and metastasis.

STUDY DESIGN, SIZE, DURATION

We conducted a prospective laboratory study in a tertiary-care university hospital. We investigated non-pregnant patients who were <42 years of age (n = 273) when they underwent surgery for a benign gynaecological condition.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The study population consisted of 102 women with histologically proven endometriosis and 71 endometriosis-free controls, who underwent a complete surgical exploration of the abdominopelvic cavity. Peritoneal fluids were collected during the surgical procedures, and endometrial and endometriotic biopsies were performed on all of the patients to generate stromal and epithelial primary cell cultures. The expression of α-2,6-sialyltransferase (ST6GALNAC1) was studied in eutopic and ectopic endometria of endometriosis patients and in eutopic endometria of controls by reverse transcription followed by quantitative real-time polymerase chain reaction (RT-qPCR). The α-2,6 sialylation levels were measured by ELISA in the peritoneal fluids of patients and controls and by western-blot in primary endometrial and endometriotic cell cultures using Sambucus nigra agglutinin (SNA), an α-2,6 sialic acid-binding lectin. A transwell migration assay after incubation of the cells with neuraminidase was also performed to evaluate the impact of desialylation on eutopic endometrial stromal cell migration.

MAIN RESULTS AND THE ROLE OF CHANCE

ST6GALNAC1 gene expression was significantly lower in endometriotic lesions compared to that in eutopic endometrium of endometriosis-affected patients and healthy endometrium (16-fold for both; P < 0.01). We observed a significant reduction in SNA levels in the peritoneal fluids of endometriosis-affected women compared to control women (median optic density (OD), 0.257; range, 0.215-0.279 versus median OD, 0.278; range 0.238-0.285; P < 0.01), as well as in stromal (mean OD, 705 907; standard error of the mean (SEM), 141 549 versus mean OD, 1.16 × 106; SEM, 107,271; P < 0.05) and epithelial (mean OD, 485 706; SEM, 179 681 versus mean OD, 1.25 × 106; SEM, 232 120; P < 0.05) ectopic endometriotic cells compared to control eutopic cells, indicating reduced α-2,6 sialylation. Finally, in the transwell migration assay, the eutopic endometrial cells of endometriosis patients migrated significantly more into the lower chamber after incubation with neuraminidase, indicating enhanced migration by these cells after desialylation.

LARGE SCALE DATA

N/A.

LIMITATIONS, REASONS FOR CAUTION

Our control group involved patients operated for benign gynaecological conditions (e.g. tubal infertility, uterine fibroids or ovarian cysts) which may also be associated with altered sialylation patterns.

WIDER IMPLICATIONS OF THE FINDINGS

The hyposialylation pattern of endometriotic cells appeared to be associated with enhanced migratory abilities, which might contribute to the establishment of early endometriotic implants. Further research is needed to confirm these findings, as this could lead to new potential therapeutic targets for this complex disorder.

STUDY FUNDING AND COMPETING INTEREST(S)

No external funding was received and there are no conflicts of interest.

Authors+Show Affiliations

Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), 53 Avenue de l'Observatoire, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), 53 Avenue de l'Observatoire, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Clinical Institute of Gynecology, Obstetrics, and Neonatology, Hospital Clinic, Universitat de Barcelona, Carrer de Villarroel, 170, Barcelona, Spain.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), 53 Avenue de l'Observatoire, Paris, France. Département 'Development, Reproduction and Cancer', Institut Cochin, INSERM U1016 (Doctor Vaiman), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d'immunologie Biologique (Professeur Batteux), 27 Rue du Faubourg Saint-Jacques, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Department of Obstetrics and Gynecology, Faculty of Medicine, Federal University of Minas Gerais, Av. Pres. Antônio Carlos, 6627 - Pampulha, Belo Horizonte, Brazil.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Département de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), 53 Avenue de l'Observatoire, Paris, France. Département 'Development, Reproduction and Cancer', Institut Cochin, INSERM U1016 (Doctor Vaiman), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France.Département 'Développement, Reproduction et Cancer', Institut Cochin, INSERM U1016 (Professeur Batteux), Université Paris Descartes, Sorbonne Paris Cité, 22 Rue Méchain, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d'immunologie Biologique (Professeur Batteux), 27 Rue du Faubourg Saint-Jacques, Paris, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30753458

Citation

Maignien, Chloé, et al. "Reduced Α-2,6 Sialylation Regulates Cell Migration in Endometriosis." Human Reproduction (Oxford, England), vol. 34, no. 3, 2019, pp. 479-490.
Maignien C, Santulli P, Chouzenoux S, et al. Reduced α-2,6 sialylation regulates cell migration in endometriosis. Hum Reprod. 2019;34(3):479-490.
Maignien, C., Santulli, P., Chouzenoux, S., Gonzalez-Foruria, I., Marcellin, L., Doridot, L., Jeljeli, M., Grange, P., Reis, F. M., Chapron, C., & Batteux, F. (2019). Reduced α-2,6 sialylation regulates cell migration in endometriosis. Human Reproduction (Oxford, England), 34(3), 479-490. https://doi.org/10.1093/humrep/dey391
Maignien C, et al. Reduced Α-2,6 Sialylation Regulates Cell Migration in Endometriosis. Hum Reprod. 2019 03 1;34(3):479-490. PubMed PMID: 30753458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced α-2,6 sialylation regulates cell migration in endometriosis. AU - Maignien,Chloé, AU - Santulli,Pietro, AU - Chouzenoux,Sandrine, AU - Gonzalez-Foruria,Iñaki, AU - Marcellin,Louis, AU - Doridot,Ludivine, AU - Jeljeli,Mohammed, AU - Grange,Philippe, AU - Reis,Fernando M, AU - Chapron,Charles, AU - Batteux,Frédéric, PY - 2018/08/07/received PY - 2018/11/22/revised PY - 2018/12/14/accepted PY - 2019/2/13/pubmed PY - 2020/7/10/medline PY - 2019/2/13/entrez KW - Sambucus nigra agglutinin KW - endometriosis KW - migration KW - pathogenesis KW - α-2,6 sialylation SP - 479 EP - 490 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 34 IS - 3 N2 - STUDY QUESTION: Is endometriosis associated with aberrant sialylation patterns and what is the potential impact of such anomalies on cell migratory properties? SUMMARY ANSWER: The reduced α-2,6 sialylation patterns in the peritoneal fluid of endometriosis-affected women and in stromal and epithelial cells from endometriotic lesions could be associated with enhanced cell migration. WHAT IS KNOWN ALREADY: Endometriosis is considered to be a benign disease although, like cancer, it has the characteristic of being an invasive disease with cells that have an enhanced capacity to migrate. Aberrant sialylation has been reported in various malignancies and it has been linked to tumour invasion and metastasis. STUDY DESIGN, SIZE, DURATION: We conducted a prospective laboratory study in a tertiary-care university hospital. We investigated non-pregnant patients who were <42 years of age (n = 273) when they underwent surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population consisted of 102 women with histologically proven endometriosis and 71 endometriosis-free controls, who underwent a complete surgical exploration of the abdominopelvic cavity. Peritoneal fluids were collected during the surgical procedures, and endometrial and endometriotic biopsies were performed on all of the patients to generate stromal and epithelial primary cell cultures. The expression of α-2,6-sialyltransferase (ST6GALNAC1) was studied in eutopic and ectopic endometria of endometriosis patients and in eutopic endometria of controls by reverse transcription followed by quantitative real-time polymerase chain reaction (RT-qPCR). The α-2,6 sialylation levels were measured by ELISA in the peritoneal fluids of patients and controls and by western-blot in primary endometrial and endometriotic cell cultures using Sambucus nigra agglutinin (SNA), an α-2,6 sialic acid-binding lectin. A transwell migration assay after incubation of the cells with neuraminidase was also performed to evaluate the impact of desialylation on eutopic endometrial stromal cell migration. MAIN RESULTS AND THE ROLE OF CHANCE: ST6GALNAC1 gene expression was significantly lower in endometriotic lesions compared to that in eutopic endometrium of endometriosis-affected patients and healthy endometrium (16-fold for both; P < 0.01). We observed a significant reduction in SNA levels in the peritoneal fluids of endometriosis-affected women compared to control women (median optic density (OD), 0.257; range, 0.215-0.279 versus median OD, 0.278; range 0.238-0.285; P < 0.01), as well as in stromal (mean OD, 705 907; standard error of the mean (SEM), 141 549 versus mean OD, 1.16 × 106; SEM, 107,271; P < 0.05) and epithelial (mean OD, 485 706; SEM, 179 681 versus mean OD, 1.25 × 106; SEM, 232 120; P < 0.05) ectopic endometriotic cells compared to control eutopic cells, indicating reduced α-2,6 sialylation. Finally, in the transwell migration assay, the eutopic endometrial cells of endometriosis patients migrated significantly more into the lower chamber after incubation with neuraminidase, indicating enhanced migration by these cells after desialylation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our control group involved patients operated for benign gynaecological conditions (e.g. tubal infertility, uterine fibroids or ovarian cysts) which may also be associated with altered sialylation patterns. WIDER IMPLICATIONS OF THE FINDINGS: The hyposialylation pattern of endometriotic cells appeared to be associated with enhanced migratory abilities, which might contribute to the establishment of early endometriotic implants. Further research is needed to confirm these findings, as this could lead to new potential therapeutic targets for this complex disorder. STUDY FUNDING AND COMPETING INTEREST(S): No external funding was received and there are no conflicts of interest. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/30753458/Reduced_α_26_sialylation_regulates_cell_migration_in_endometriosis_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dey391 DB - PRIME DP - Unbound Medicine ER -