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Generation of high-throughput three dimensional tumor spheroids for drug screening

Mathews Griner, Lesley and Gampa, Kalyani and Do, Toan and Hartkopf, Huyen and Farley, David and Auld, Douglas and Silver-Brown, Serena (2018) Generation of high-throughput three dimensional tumor spheroids for drug screening. Generation of high-throughput three dimensional tumor spheroids for drug screening , 3 (139).

Abstract

Cancer cells have routinely been cultured in 2-dimensions (2D) on a plastic surface. This technique, however, lacks the true environment a tumor mass is exposed to in vivo. Solid tumors grow not as a sheet attached to plastic, but instead as aggregated cells in three dimensions interacting with their neighbors, and with distinct spatial properties such as polarity. These interactions cause the three dimensional (3D) cultured cells to acquire morphological and cellular characteristics which are more relevant to in vivo tumors1. Additionally, a tumor mass is in direct contact with other cell types such as stromal and immune cells, as well as extracellular matrix from all other cell types. The matrix which is deposited is comprised of macro-molecules such as collagen and fibronectin. In an attempt to increase the translation of research findings in oncology from the bench to the bedside many groups have started to investigate the use of three dimensional (3D) model systems in their drug development strategies. These systems are thought to be more physiologically relevant because they attempt to recapitulate the complex and heterogeneous environment of a tumor1 These systems, however, can be quite complex, and although amenable to growth in 96-well formats, and some now even in 384, offer few choices for large scale growth and screening. This observed gap has led to the development of the methods described here in detail to culture tumor spheroids in a high throughput capacity in 1536-well plates. A variety of cancer cell lines were successfully screened examining compound efficacy using a curated library of compounds targeting the MAPK pathway. The spheroid culture responses were then compared to the response of cells grown in 2D and differential activities are reported. These methods provide a unique protocol for testing compound activity in a high-throughput 3D setting.

Item Type: Article
Date Deposited: 01 Dec 2018 00:45
Last Modified: 01 Dec 2018 00:45
URI: https://oak.novartis.com/id/eprint/34369

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