A well-defined in vitro three-dimensional culture of human endometrium and its applicability to endometrial cancer invasion.
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 alpha1, alpha4, and beta3 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.
Park
Dong Wook
DW
Department of Molecular Science and Technology, Ajou University, Suwon 442-749, South Korea.
Choi
Dong Soon
DS
Ryu
Hee-Sug
HS
Kwon
Hyuck Chan
HC
Joo
Hyun
H
Min
Churl K
CK
D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000737:chemistry / Q000166:cytology; D003094:Collagen; D024042:Collagen Type I; D003470:Culture Media; D046508:Culture Techniques / Q000379:methods*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004338:Drug Combinations; D016889:Endometrial Neoplasms / Q000473:pathology*; D004717:Endometrium / Q000737:chemistry / Q000166:cytology*; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology; D005260:Female; D006801:Humans; D039423:Integrin alpha1 / Q000032:analysis; D039441:Integrin alpha4 / Q000032:analysis; D039661:Integrin beta3 / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D007633:Keratins / Q000032:analysis; D007797:Laminin; D020782:Matrix Metalloproteinases / Q000032:analysis; D008565:Membrane Proteins; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D011509:Proteoglycans; D017154:Stromal Cells / Q000737:chemistry / Q000166:cytology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
D024042:Collagen Type I; D003470:Culture Media; D004338:Drug Combinations; D039423:Integrin alpha1; D039661:Integrin beta3; D007527:Isoenzymes; D007797:Laminin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; C059485:matrigel; D019716:Tissue Inhibitor of Metalloproteinase-2; D039441:Integrin alpha4; D007633:Keratins; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020782:Matrix Metalloproteinases