Volumetric analysis of the terminal ductal lobular unit architecture and cell phenotypes in the human breast
Oona Paavolainen,
Markus Peurla,
Leena M. Koskinen,
Jonna Pohjankukka,
Kamyab Saberi,
Ella Tammelin,
Suvi-Riitta Sulander,
Masi Valkonen,
Larissa Mourao,
Pia Boström,
Nina Brück,
Pekka Ruusuvuori,
Colinda L.G.J. Scheele,
Pauliina Hartiala,
Emilia Peuhu
Affiliations
Oona Paavolainen
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Markus Peurla
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Leena M. Koskinen
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Jonna Pohjankukka
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Kamyab Saberi
VIB Center for Cancer Biology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium
Ella Tammelin
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Suvi-Riitta Sulander
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Masi Valkonen
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland
Larissa Mourao
VIB Center for Cancer Biology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium
Pia Boström
Department of Pathology, Turku University Hospital, 20520 Turku, Finland; University of Turku, 20520 Turku, Finland
Nina Brück
Department of Pathology, Turku University Hospital, 20520 Turku, Finland; University of Turku, 20520 Turku, Finland
Pekka Ruusuvuori
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland
Colinda L.G.J. Scheele
VIB Center for Cancer Biology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium
Pauliina Hartiala
University of Turku, 20520 Turku, Finland; Department of Plastic and General Surgery, Turku University Hospital, 20520 Turku, Finland; Medicity Research Laboratories and InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
Emilia Peuhu
Institute of Biomedicine, Cancer Laboratory FICAN West, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Corresponding author
Summary: The major lactiferous ducts of the human breast branch out and end at terminal ductal lobular units (TDLUs). Despite their functional and clinical importance, the three-dimensional (3D) architecture of TDLUs has remained undetermined. Our quantitative and volumetric imaging of healthy human breast tissue demonstrates that highly branched TDLUs, which exhibit increased proliferation, are uncommon in the resting tissue regardless of donor age, parity, or hormonal contraception. Overall, TDLUs have a consistent shape and branch parameters, and they contain a main subtree that dominates in bifurcation events and exhibits a more duct-like keratin expression pattern. Simulation of TDLU branching morphogenesis in three dimensions suggests that evolutionarily conserved mechanisms regulate mammary gland branching in humans and mice despite their anatomical differences. In all, our data provide structural insight into 3D anatomy and branching of the human breast and exemplify the power of volumetric imaging in gaining a deeper understanding of breast biology.
