Zero to one: normal derived human ER+ cells in culture-proliferating

TY - JOUR

T1 - Zero to one

T2 - normal derived human ER+ cells in culture-proliferating

AU - Hopkinson, Branden Michael

PY - 2016

Y1 - 2016

N2 - Cell culture technology is used to model structural and functional properties of human organs under normal and pathological conditions “in a dish”. The most obvious reason to culture human breast-derived cells is our fundamental desire to understand and ultimately treat breast cancer. Highly reproducible serum-free formulations for long-term propagation of normal human breast epithelial cells have existed for more than three decades and have served to complement the insight gained from a vast number of established breast cancer cell lines. The unspoken dichotomy in the experimental approach however has lied in the puzzling fact that normal-derived cells show a more myoepithelial expression profile, while breast cancer cells show more of a luminal profile making these difficult to compare experimentally. Moreover, normal estrogen receptor positive (ER+) luminal cells, thought to be equivalents to the most frequent form of human breast cancer, the ER+ subtype, completely fail to grow under standard culture conditions. This fact could be overlooked since breast homeostasis relies on a stem cell hierarchy and stem cells reside in the myoepithelial compartment which, if given the right conditions, can differentiate into ER+ luminal cells. The problem with this approach is that myoepithelial cells in culture, for unknown reasons, fail to behave like myoepithelial cells in vivo. This review summarizes some of the progress that has been made in the field with regard to the ER+ luminal breast epithelial lineage, especially within a human context, and its relevance to human breast cancer.

AB - Cell culture technology is used to model structural and functional properties of human organs under normal and pathological conditions “in a dish”. The most obvious reason to culture human breast-derived cells is our fundamental desire to understand and ultimately treat breast cancer. Highly reproducible serum-free formulations for long-term propagation of normal human breast epithelial cells have existed for more than three decades and have served to complement the insight gained from a vast number of established breast cancer cell lines. The unspoken dichotomy in the experimental approach however has lied in the puzzling fact that normal-derived cells show a more myoepithelial expression profile, while breast cancer cells show more of a luminal profile making these difficult to compare experimentally. Moreover, normal estrogen receptor positive (ER+) luminal cells, thought to be equivalents to the most frequent form of human breast cancer, the ER+ subtype, completely fail to grow under standard culture conditions. This fact could be overlooked since breast homeostasis relies on a stem cell hierarchy and stem cells reside in the myoepithelial compartment which, if given the right conditions, can differentiate into ER+ luminal cells. The problem with this approach is that myoepithelial cells in culture, for unknown reasons, fail to behave like myoepithelial cells in vivo. This review summarizes some of the progress that has been made in the field with regard to the ER+ luminal breast epithelial lineage, especially within a human context, and its relevance to human breast cancer.

U2 - 10.14800/rci.1449

DO - 10.14800/rci.1449

M3 - Review

SN - 2330-0566

VL - 3

JO - Receptors & Clinical Investigation

JF - Receptors & Clinical Investigation

IS - 4

M1 - e1449

ER -