A well-defined in vitro three-dimensional culture of human endometrium and its applicability to endometrial cancer invasion

• Published in: Cancer letters 2003-06, Vol.195 (2), p.185-192
• Main Authors: Park, Dong Wook, Choi, Dong Soon, Ryu, Hee-Sug, Kwon, Hyuck Chan, Joo, Hyun, Min, Churl K
• Format: Article
• Language: English
• Subjects: 3-dimensional culture; Biological and medical sciences; Cancer invasion; Cell Communication; Cell culture; Cell Differentiation; Cells, Cultured - chemistry; Cells, Cultured - cytology; Collagen; Collagen Type I; Culture Media; Culture Techniques - methods; Cyclooxygenase 1; Cyclooxygenase 2; Drug Combinations; Endometrial cancer; Endometrial Neoplasms - pathology; Endometrium - chemistry; Endometrium - cytology; Epithelial Cells - chemistry; Epithelial Cells - cytology; Female; Human endometrium; Humans; Integrin alpha1 - analysis; Integrin alpha4 - analysis; Integrin beta3 - analysis; Isoenzymes - analysis; Keratins - analysis; Laminin; Matrix metalloproteinase; Matrix Metalloproteinases - analysis; Medical sciences; Membrane Proteins; Microscopy; Microscopy, Electron; Microscopy, Electron, Scanning; Neoplasm Invasiveness; Neoplasm Proteins - analysis; Prostaglandin-Endoperoxide Synthases - analysis; Proteoglycans; Rodents; Steroids; Stromal Cells - chemistry; Stromal Cells - cytology; Studies; Tissue inhibitor of metalloproteinase; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-2 - analysis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(03)00131-9

A three-dimensional (3-D) endometrium culture was established, in which human endometrial stromal cells embedded in a mixture of collagen I, a major component of extracellular matrix, and matrigel, a basement membrane material, supports the epithelial cells seeded on top of the collagen/matrigel matrix. The biological growth and differentiation of the epithelial cells were studied microscopically and immunohistochemically. Transmission electron microscopy showed a polarized columnar epithelium in monolayer with basally positioned nuclei. Scanning electron microscopy revealed a confluent epithelium with an abundance of microvilli and cilia as well as pinopodes on the apical surface. An immunohistochemical staining showed that integrin α1, α4, and β3 were co-localized with cytokeratin, confirming the epithelial origin of the cells. In contrast, immunoreactivity against cyclooxygenase-1 or -2 was positive in both epithelial and stromal cells. When epithelial cells were replaced by KLE cells, an endometrial cancer cell of epithelial origin, invasion of KLE cells into the stromal fraction was observed. The invasion was closely correlated to expression of matrix metalloproteinases and their tissue inhibitors of metalloproteinases in a manner consistent with paracrine fashion. The present 3-D culture imitates the normal endometrium physiologically as well as morphologically, thus provides an excellent in vitro tissue suitable for reproducing in vivo physiological processes, including endometrial cancer invasion.