RT Journal Article
SR Electronic
T1 A new analytical pipeline for the study of the onset of mammary gland oncogenesis based on mammary organoid transplantation and organ clearing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 860270
DO 10.1101/860270
A1 Emilie Lagoutte
A1 Clémentine Villeneuve
A1 Vincent Fraisier
A1 Denis Krndija
A1 Marie-Ange Deugnier
A1 Philippe Chavrier
A1 Carine Rossé
YR 2019
UL http://biorxiv.org/content/early/2019/11/30/860270.abstract
AB Metastasis formation is a multi-step process starting from the dissemination of transformed carcinomatous cells from the primary tumor and could occur at a very early stage of oncogenesis, before primary tumor detection. The adult mammary gland provides a unique model to investigate epithelial cell dissemination processes. Tissue clearing techniques allow imaging samples of large volume. uDSICO clearing, one of the latest tissue clearing technique developed, provides optical imaging of whole organ due to organ clearing and tissue size reduction. We wanted to take advantage of this technique to study rare events occurring in vivo.Here, we have established a new analytical pipeline exploiting the regenerative properties of the mammary epithelium following orthotropic transplantation of organoids together with the uDISCO organ size reduction and clearing method to study early cell dissemination in the mammary gland. As proof of concept, we analyzed the localization of epithelial cells overexpressing the oncogenic protein atypical protein kinase C iota (aPKCi+) in the normal mammary gland and we were able to visualize epithelial aPKCi+ cells, surrounded by normal epithelial cells, escaping from the normal mammary epithelium and disseminating into the surrounding stroma.