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Micrometastasis of endometriosis to distant organs in a murine model

Elham N. Samani, Ramanaiah Mamillapalli _, Fei Li, Levent Mutlu, Demetra Hufnagel, Graciela Krikun and Hugh S. Taylor

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Oncotarget. 2019; 10:2282-2291. https://doi.org/10.18632/oncotarget.16889

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Abstract

Elham N. Samani1, Ramanaiah Mamillapalli1, Fei Li1, Levent Mutlu1, Demetra Hufnagel1, Graciela Krikun1 and Hugh S. Taylor1

1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, Connecticut 06510, New Haven, USA

Correspondence to:

Ramanaiah Mamillapalli, email: [email protected]

Keywords: endometriosis, micrometastasis, DsRed cells, metastasis, mice

Received: January 13, 2017     Accepted: March 30, 2017     Epub: April 06, 2017     Published: March 19, 2019

ABSTRACT

Endometriosis is an inflammatory gynecological disorder among reproductive-aged women caused by the engraftment and proliferation of endometrial cells outside the uterus, most commonly in the pelvis. It is thought that the disease arises primarily from retrograde menstruation where cells from the endometrium travel through the fallopian tubes to the peritoneal cavity. However, migration of endometriosis-derived cells to distant organs outside of the peritoneal cavity have not been explored. In the present study, we developed and validated a mouse model of disseminated endometriosis using syngeneic DsRed endometrial tissue introduced into the peritoneum of immunocompetent mice. Flow cytometry and immunofluorescence analysis, demonstrated the presence of endometriosis-derived cells in multiple organs (including lung, spleen, liver and brain) in the murine endometriosis model. Immunostaining revealed the presence of DsRed+/CD45 cells in brain, liver and lung. Engraftment occurred in all experimental animals examined. Cells from endometriotic lesions are capable of migration to and engraftment of multiple organs outside of the peritoneal cavity. Micrometastasis of endometriosis is a novel and frequent phenomenon. These data suggest that widespread dissemination of endometriosis may be common, clinically unrecognized and contribute to the diffuse clinical manifestations of this disease.


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