Methods of Cancer Diagnosis, Therapy, and Prognosis

"13 Translating In Vitro Cell Lines Result into Clinical Practice (p. 183-184)

Jai Prakash Mehta, Lorraine O’Driscoll, Niall Barron, Martin Clynes, and Padraig Doolan

INTRODUCTION

Immortalized cell lines provide an easy and convenient option for analysis of biological systems compared to clinical specimens. Cell culture has gained wide popularity in the study of cancer, because of the innate continuously proliferating nature of these cell lines. Cancer cell lines are obtained by the enzymatic digestion or explant growth of tumour specimens. The main advantage of using cell lines for such research is the immortal nature of the cell lines, enabling them to be continuously cultured, distributed and studied in many labs and to act as a reliable platform for comparison of results, before advancing research to the next level.

Another advantage of performing research on cell lines is ease of handling and storage. Cell lines are cultured in flasks under well-controlled nutritional and environmentalal conditions and this ensures a greater degree of reproducibility in the results. Some assays require large amount of material; with cell line models, this is generally not a constraint. Cells can be stored indefinitely in liquid nitrogen and can be used when needed. Apart from the ease in maintenance and access, cell lines offer a convenient platform for genetic manipulation of cells. Many recent studies in cancer have centered on functional aspects of gene expression changes.

Cell lines offer a realistic platform to knockdown or over-express genes of interest. Due to the tremendous benefits of working on cell lines, they have dramatically contributed to basic research in cancer biology. Recent interest has focused on extrapolating the relevance of findings from cell line models to clinical models. There are obvious differences between cell line models and clinical specimens due to the difference in environments to which they have been exposed. These differences need to be accurately defined for the results arising from the cell line studies to be clinically relevant.

A detailed study on these differences will help researchers to decide on the applicability of cell line models for their particular study and will pave the way in making the results more accurate and relevant to that of clinical condition. This manuscript examines the differences between cell line models and clinical specimens, particularly focusing on breast cancer. HOw CeLL LINeS ARe GeNeRATeD enzymatic digestion: Tumour tissue is digested using enzymes such as collagenase, trypsin, or pronase.

These enzymes break down the extracellular matrix, thereby releasing the cells which are subsequently cultured in nutrient rich medium and in a controlled environment (Doyle et al. 1998). explant culture: Small pieces of tissue are placed in nutrient rich medium and the cells that grow out and migrate from the primary tissue are further cultured (Doyle et al. 1998). TyPeS Of CeLL CuLTuRe Primary cultures: Cells obtained directly from the tissue are termed primary cultures.

Primary cultures have a defined life span and undergo a process of senescence and stop dividing, while remaining viable for short time period. Studies done on primary cultures can be very useful as these cells have not been in culture for long time after procuring from the body/ in vivo condition. However, primary culture has its own limitations. Since primary cultures cannot be maintained in culture for extended periods, lengthy experiments may be challenging; these cells generally cannot be distributed to other labs; and the experiments performed cannot be repeated at a later date to determine reproducibility."