Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation.
The reproductive role of the fallopian tube is to transport the sperm and egg. The tube is positioned to act as a bridge between the ovary where the egg is released and the uterus where implantation occurs. Throughout reproductive years, the fallopian tube epithelium undergoes repetitive damage and regeneration. Although a reservoir of adult epithelial stem cells must exist to replenish damaged cells, they remain unidentified. Here, we report isolation of a subset of basally located human fallopian tube epithelia (FTE) that lack markers of ciliated (β-tubulin; TUBB4) or secretory (PAX8) differentiated cells. These undifferentiated cells expressed cell surface antigens: epithelial cell adhesion molecule, CD44, and integrin α 6. This FTE subpopulation was fivefold enriched for cells capable of clonal growth and self-renewal suggesting that they contain the FTE stem-like cells (FTESCs). A twofold enrichment of the FTESC was found in the distal compared to the proximal end of the tube. The distal fimbriated end of the fallopian tube is a well-characterized locus for initiation of serous carcinomas. An expansion of the cells expressing markers of FTESC was detected in tubal intraepithelial carcinomas and in fallopian tubes from patients with invasive serous cancer. These findings suggest that FTESC may play a role in the initiation of serous tumors. Characterization of these stem-like cells will provide new insight into how the FTE regenerate, respond to injury, and may initiate cancer.
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Daniel Y
DY
Paik
Deanna M
DM
Janzen
Amanda M
AM
Schafenacker
Victor S
VS
Velasco
May S
MS
Shung
Donghui
D
Cheng
Jiaoti
J
Huang
Owen N
ON
Witte
Sanaz
S
Memarzadeh
D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D002277:Carcinoma / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005185:Fallopian Tube Neoplasms / Q000473:pathology*; D005187:Fallopian Tubes / Q000473:pathology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D018874:Spheroids, Cellular / Q000502:physiology
D000951:Antigens, Neoplasm; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors