M2 macrophages enhance endometrial cell invasiveness by promoting collective cell migration in uterine adenomyosis

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M2 macrophages accumulate in adenomyosis and enhance endometrial cell invasiveness by promoting collective cell migration, independent of epithelial-mesenchymal transition.

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This study investigated whether M2 macrophages are implicated in endometrial invasiveness in uterine adenomyosis by analyzing 17 formalin-fixed paraffin-embedded uterine samples and 16 fresh endometrial biopsies from women with or without adenomyosis. Using double immunofluorescence, the authors found that only M2 macrophages accumulated in adenomyosis, with higher numbers in eutopic endometrium and in lesions than in healthy tissue, and that co-culture with M2 macrophages increased the invasion capacity of both epithelial and stromal endometrial cells from adenomyosis patients and healthy controls. In evaluating mechanism, they reported no detectable gene expression differences consistent with epithelial-mesenchymal transition, and they observed that E- and N-cadherin protein expression was not significantly different overall, although MMP9 was increased in eutopic stroma and E- and N-cadherin were more extensively expressed in basal glands, suggesting collective cell migration rather than EMT. This paper is centrally about adenomyosis—specifically how M2 macrophage accumulation enhances endometrial cell invasiveness via collective migration.

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M2 macrophages enhance endometrial cell invasiveness by promoting collective cell migration in uterine adenomyosis. (2023) Reproductive BioMedicine Online — Vol. 46, n° 4, p. 729-738 (2023) (2023) Reproductive BioMedicine Online — Vol. 46, n° 4, p. 729-738 (2023) Open Access - Adobe PDF - 3.63 MB - Authors - Author Stratopoulou, Christina Anna UCLouvain - Author Cussac, Sophie UCLouvain - Author d'Argent, Marie UCLouvain - Author Donnez, Jacques - Author - Abstract - (en) RESEARCH QUESTION: Are M2 macrophages implicated in endometrial invasiveness in adenomyosis? DESIGN: Seventeen formalin-fixed paraffin-embedded uterine samples and 16 fresh endometrial biopsies were collected from women with or without adenomyosis. Double immunofluorescence was performed to determine the predominant macrophage population in adenomyosis between M1 and M2 phenotypes. The invasion capacity of endometrial cells was assessed by invasion assays and quantitative polymerase chain reaction for genes involved in cell motility and epithelial-mesenchymal transition (EMT). Specific mechanisms of invasion were investigated by immunohistochemistry for E-cadherin, N-cadherin and matrix metalloproteinase 9 (MMP9). RESULTS: Only M2 macrophages were found to accumulate in adenomyosis, in higher numbers in both eutopic endometrium (P = 0.0109) and lesions (P = 0.0267) than healthy tissue. Co-culture with M2 macrophages significantly boosted invasion capacity in endometrial epithelial (P = 0.0002; P = 0.002) and stromal cells (P = 0.0469; P = 0.0047) from both adenomyosis patients and healthy controls. No gene expression differences indicating EMT were noted, either between co-cultured and control cells, or between healthy and adenomyotic cells. E- and N-cadherin protein expression did not differ significantly between endometrium from adenomyosis subjects and healthy tissue but MMP9 expression was increased in eutopic stroma from adenomyosis patients (P = 0.0492). In adenomyosis, both E-cadherin (P = 0.0379) and N-cadherin (P = 0.0196) were more extensively expressed in basal glands than functional glands. CONCLUSIONS: M2 macrophages accumulate in adenomyosis and enhance invasion capacity of adenomyotic and even healthy endometrial cells, implying that macrophage infiltration alone may be sufficient to promote the disease. This study failed to detect any changes pointing to EMT, suggesting an alternative mode of invasion. Strong E- and N-cadherin-positive intercellular junctions in basal (invasive) glands suggest the involvement of collective cell migration in the invasion process of endometrium. - Affiliations - APA - Chicago - FWB Stratopoulou, C. A., Cussac, S., d’Argent, M., Donnez, J., & Dolmans, M.-M. (2023). M2 macrophages enhance endometrial cell invasiveness by promoting collective cell migration in uterine adenomyosis. Reproductive BioMedicine Online, 46(4), 729-738. https://doi.org/10.1016/j.rbmo.2023.01.001 (Original work published 2023)

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Condition tags

mesh:D004715adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

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