Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium.
BACKGROUND
Basoapical polarity in epithelia is critical for proper tissue function, and control of proliferation and survival. Cell culture models that recapitulate epithelial tissue architecture are invaluable to unravel developmental and disease mechanisms. Although factors important for the establishment of basal polarity have been identified, requirements for the formation of apical polarity in three-dimensional tissue structures have not been thoroughly investigated.


RESULTS
We demonstrate that the human mammary epithelial cell line-3522 S1, provides a resilient model for studying the formation of basoapical polarity in glandular structures. Testing three-dimensional culture systems that differ in composition and origin of substrata reveals that apical polarity is more sensitive to culture conditions than basal polarity. Using a new high-throughput culture method that produces basoapical polarity in glandular structures without a gel coat, we show that basal polarity-mediated signaling and collagen IV are both necessary for the development of apical polarity.


CONCLUSIONS
These results provide new insights into the role of the basement membrane, and especially collagen IV, in the development of the apical pole, a critical element of the architecture of glandular epithelia. Also, the high-throughput culture method developed in this study should open new avenues for high-content screening of agents that act on mammary tissue homeostasis and thus, on architectural changes involved in cancer development.
Plachot
Cedric
C
Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. cplachot@luminexcorp.com
Chaboub
Lesley S
LS
Adissu
Hibret A
HA
Wang
Lei
L
Urazaev
Albert
A
Sturgis
Jennifer
J
Asem
Elikplimi K
EK
Lelièvre
Sophie A
SA
D001485:Basement Membrane / Q000378:metabolism; D001940:Breast; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D024141:Collagen Type IV / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000502:physiology; D015398:Signal Transduction; D018874:Spheroids, Cellular
D024141:Collagen Type IV