• The Boekelheide lab has a developed a 3D microtissue of the human breast. The microtissue is comprised of human breast cancer cells.
• These cells aggregate to form a single 3D microtissue that then undergoes an additional and dramatic morphological change. The single initial microtissue forms several smaller clusters of cells, each with a lumen or hollow space. Each lumen is surrounded by a cell layer 1-2 cells thick.
• We used a periodic acid-Schiff stain and showed that carbohydrate-positive material is being secreted into the lumens. Electron microscopy revealed the presence of microvilli, small finger-like cellular projections on the interior surface of the lumens.
• This demonstrates that in addition to morphogenesis, the cells are undergoing polarization, with their apical surface facing the luminal space and their basal-like surface facing the exterior of the microtissue.
• We also showed that the breast microtissues have strong staining for mucin 1 and milk fat globule-EGF factor 8 protein and strong staining for E-cadherin localized to the cell-cell contacts.
• A comparison of gene and protein expression between cells in a 2D monolayer versus the same cells in a 3D microtissue showed that the 3D environment significantly enhanced the expression of genes associated with differentiation and more closely mimicked that of breast tissue.
• To determine if the breast microtissues were responsive to hormone, we treated the microtissues with 17β-estradiol for 8 hours, and analyzed the expression of genes known to be targets of estrogen. Treatment with 17β-estradiol caused a dose-dependent increase in expression of the GREB gene (growth regulation by estrogen in breast cancer 1) and the PGR gene (progesterone receptor).
• We are using human breast 3D microtissues to investigate the toxicological effects of estrogens and chemicals that mimic estrogenic’s effects.

Vantangoli, M. M., Wilson, S., Madnick, S. J., Huse, S. M., & Boekelheide, K. (2016). Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues. Toxicology Letters, 248, 1-8. PMC4803074

Vantangoli, M. M., Madnick, S. J., Wilson, S., & Boekelheide, K. (2016). Estradiol exposure differentially alters monolayer versus microtissue MCF-7 human breast carcinoma cultures. PLoS One, 11(7), e0157997. PMC4933361 

Vantangoli, M. M., Madnick, S. J., Huse, S. M., Weston, P., & Boekelheide, K. (2015). MCF-7 Human breast cancer cells form differentiated microtissues in scaffold-free hydrogels. PLoS One, 10(8), e0135426. PMC4534042