title: Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context.
abstract: Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to inducein vitrolesion formation in order to identify soluble factors that influence proliferation and invasion.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53706.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Pollock
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53706.
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Jaraczewski
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53706.
authors.forename: Molly J
authors.initials: MJ
authors.lastname: Carroll
authors.affiliation: Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave., Madison, WI, 53705.
authors.forename: Dan I
authors.initials: DI
authors.lastname: Lebovic
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53706.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Kreeger
keywords: 3D culture; CXCL8; Heparin-binding EGF-like growth factor (HB-EGF); basement membrane; endometriosis