Tumor Cell Lines Sometimes an Alternative

Compared to primary cells, permanent cell lines would represent continuous, stable and rather homogeneous test systems. Nevertheless, cell lines are - with few exceptions - less popular metabolic models. Of the available liver cell lines, only in HepG2 (the dominant cell line in drug metabolism) and in the more recently identified hepatoma BC2, can phase I and II enzymes be induced, while basal activity remains very low (reviewed in [8]).

The human Caco-2 cell line, developed from an intestinal carcinoma, is a valuable model for the study of metabolic and transport parameters in the human intestine with induction of major intestinal P450 CY3A4 [9-11]. Cell lines typically originate from naturally occurring tumors, are often dedifferentiated, and show only a fraction of the physiologic response. A very few cell lines can be redifferentiated under appropriate culture conditions. As an example, Ntera2 [12] can generate postmitotic neurons expressing multiple specific markers [13] and even forming neuronal networks [14]. The differentiation of liver cell lines remains challenging, and has yielded only limited success; the search for highly differentiated hepatic tumors continues [15].

The differentiation of embryonic stem cells (ESC) in vitro could provide an unlimited supply for cell types of interest using the replicative potential of the starter cell. Ethical concerns against the use of ESC have prevented widespread routine generation of cellular models in drug testing from stem cells. Recent findings that adult mouse spermatogonial stem cells (SSC) can obtain ESC-like features and differentiate into derivatives of the three different germ layers may provide an ethical alternative to ESC if transferable to human SSC [16].

Designing cell lines by the immortalization of primary cells using known mechanisms is another viable alternative. While this approach also represents substantial challenges, it offers not only well-defined, unlimited test material but also the potential for generating sets of similar cell lines on variable genetic background for studies in a pharmacogenomic context.

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