Role of Biorepositories in Personalized Medicine: Isolation and Processing of Primary Tumor Cells for the initiation Tumor Cultures

Zhang H,Wang J,Liang Z,Moore W,Ma J

doi:10.31579/2640-1053/009

Abstract

The introduction of three-dimensional (3D) tumor cultures has revolutionized anticancer drug research as these cultures allow for the study of drug resistance mechanisms that cannot be explored in traditional two dimensional (2D) monolayer cultures. Discoveries in the 3D tumor culture field suggest that individualized drug sensitivity testing of solid tumor specimens through the establishment and use of 3D tumor cell cultures following tissue collection will become a routine service offered by modern tissue repositories as they expand from their traditional research role to active participation in personalized medicine. Unfortunately, most information related to 3D tumor cultures comes from studies using established tumor cell lines rather than primary tumor cultures. However, accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine. There is only very limited information available concerning technologies and standard operating procedures for the efficient and routine isolation and processing of primary tumor cells for the establishment of 3D tumor cultures from solid tumor specimens. The purpose of this work was to review experimental data from the literature that may provide relevant information concerning the isolation and processing of primary tumor cells for the establishment of 3D tumor cultures. Information reviewed here may help bio repositories in the development and standardization of technologies and standard operating procedures related to the use of 3D tumor cultures.

Highlights

Accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine [1,2]
Observations suggest that individualized drug sensitivity testing of solid tumors through the isolation and culturing primary tumor cells in 3D may soon become routine and modern tissue repositories will need to be ready to support these activities as they expand from their traditional research role to active participation in personalized medicine [5]
These relate to colorectal, lung and brain tumors indicating that isolation and growth of primary tumors cells in 3D cultures is possible for a variety of solid tumors

Summary

Introduction

Accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine [1,2]. The critical importance of technologies related to the derivation, short term culture, and testing of primary tumor cells from solid tumors is increasingly recognized (for a recent review see 2). Short-term primary cultures of tumor cells derived from pieces of solid tumors have been used for predicting anticancer drug responses [3,4]. Observations suggest that individualized drug sensitivity testing of solid tumors through the isolation and culturing primary tumor cells in 3D may soon become routine and modern tissue repositories will need to be ready to support these activities as they expand from their traditional research role to active participation in personalized medicine [5]. Cancer cells grown in 3D cultures in a polymeric ECM closely mimic the biology of tumor development in vivo and numerous studies indicate that 3D cultures are superior to traditional 2D monolayer cultures for studies of key cellular behaviors like differentiation, proliferation, invasion and apoptosis [6-8]. Cancer cells grown in 3D culture are more resistant to chemotherapeutic agents, radiation and oncolytic virotherapy than cells in 2D culture and 3D tumor cell cultures are useful for preclinical evaluation of the cytotoxic effect of anticancer agents [6, 9-16]

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