The practicalities of using tissue slices as preclinical organotypic breast cancer models

Abstract

Models considering breast cancer complexity cannot be easily or accurately replicated in routine cell line or animal models. We aimed to evaluate the practicality of organotypic tissue slice culture in breast cancer. Following ethical approval, 250 µm thick sections from surplus breast tumours (n=10) were prepared using a vibrating blade microtome. Triplicate tissue slices were placed in 6-well plates and cultured for up to 7 days ± tamoxifen (1 nM) or doxorubicin (1 µM). Tissue slices were fixed and embedded before sectioning for morphological evaluation and immunohistochemistry. H&E showed good preservation of tissue morphology. Collagen production was evident. Biomarkers of proliferation and apoptosis could be evaluated using immunohistochemistry and used as surrogates to quantify drug effects. In summary, breast cancer tissue slices can be cultured in vitro as organotypic models. Nevertheless, although simple in concept, the delicacy of the model with regard to handling makes subsequent analytical processes challenging.

Precision Oncology: The Road Ahead

“…soft, mucinous or fatty tissue), where firm tissue consistency is required [213, 214]. Another drawback of slice cultures is the loss of viability within 5 to 7 days [211].…”

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

“…This allows a more accurate prediction of the human in vivo cell behavior. Tissue slices were applied to cancer research in order to analyze therapeutic strategies and drug responses, as well as to gain new insight into the cell invasion process [131][132][133].…”

“…In this case neurospheres have been implanted on the center of human [133] or rat brain slices [222]. The histological evaluation of the confrontation revealed either an invasive pattern or a non-invasive pattern (see the relevant paragraph for a better description).…”

“…In the noninvasive pattern the tumor-derived cells live together with, and generally surround the host tissue without replacing or destroying it, as seen with non-invasive benign meningioma [253,254]. Several upgraded protocols have been proposed, which consist in implanting fluorescent stained spheroids, obtained from human brain tumors, on the center of human [133], or rat brain slices [222]. The invasion process can be evaluated over the time by using a confocal microscopy.…”

“…The invasion process can be evaluated over the time by using a confocal microscopy. The advantages consist in a better representation of the invasion process, due to the fluorescent tag applied to the tumor cells, as well as in a better representation of extracellular matrix molecules normally encountered by invading glioma cells [133,222]. Oellers and collaborators described a similar refined protocol [255], presenting a co-culture of glioma cells with myelinated axons in vitro, with the aim to study the interactions between migrating glioma cells and nerve fibers.…”