Affiliation:
1. NMI – Natural and Medical Sciences Institute at the University of Tuebingen
2. Department of Women's Health, Eberhard Karls University Tuebingen
Abstract
Abstract
Background
Tumor-adjacent benign mammary epithelium and myoepithelium can play a pivotal role in tumor growth and progression. We investigated the invasive behavior of patient-derived microtumors and breast cancer cell line-derived spheroids in co-culture with induced pluripotent stem cell-derived mammary-like organoids in an autologous and allogenic manner. This co-culture systems enables a better understanding of the tumor-promoting function of the benign mammary (myo-) epithelium in different types of breast cancers.
Methods
Using three-dimensional co-culture settings of induced pluripotent stem cell-derived mammary-like organoids and patient-derived microtumors or cancer cell line-derived spheroids, we investigated tumor growth and invasiveness of the cancers by using imaging-based analysis. Levels of Fibronectin and Metalloproteinase-2 in co-cultures and respective mono-cultures were measured using multiplexed Luminex assay.
Results
We observed significant increases in growth and invasiveness of invasive ductal carcinoma of no special type patient-derived microtumors in co-culture with induced pluripotent stem cell-derived mammary-like organoids. We identified upregulations of the prognostic markers Fibronectin and Metalloproteinase-2 in all co-cultures compared to respective mono-cultures of mammary-like organoids, patient-derived microtumors and cell line-derived spheroids.
Conclusions
These findings indicate a tumor-promoting role of the tumor-adjacent mammary (myo-) epithelium dependent on the tumor composition and tumor stage. Our results highlight the importance of breast tumor models that closely resemble the heterogenous composition of primary breast tumors.
Publisher
Research Square Platform LLC