New publication in EMBO Journal
Cancer organoids fancy a different milieu to thrive
In collaboration with scientists from the Charité, we investigated under which conditions human ovarian cancer cells thrive. For that purpose, we compared normal fallopian tube organoids to two models of ovarian cancer organoids: 1) organoids established from primary ovarian cancer samples and 2) organoids established from healthy fallopian tube samples, in which we knocked-down the tumor-suppressing genes, p53, PTEN and RB, known to be involved in early carcinogenesis. It appears that cancer organoids favor a low Wnt environment to expand, in contrast to healthy organoids that favor a Wnt-rich environment. Active BMP signaling is also a favorable condition for the expansion of cancer organoids. When deprived of these conditions, cancer organoids display a partial differentiation and growth-arrest phenotype. In conclusion, not only mutagenesis, but also tumor microenvironment is a major cancer transformation driver.
Hoffmann K, Berger H, Kulbe H, Thillainadarasan S, Mollenkopf HJ, Zemojtel T, Taube E, Darb-Esfahani S, Mangler M, Sehouli J, Chekerov R, Braicu EI, Meyer TF and Kessler M Stable expansion of high-grade serous ovarian cancer organoids requires a low-Wnt environment. EMBO J (2020)