How do you effectively choose a cell line for murine xenografts? What information is needed to effectively compare several cell lines? Is there a way to predict what cell lines will produce larger tumors faster; or what cancer line will be more robust and proliferate in unideal conditions?
B16F10 (murine melanoma) works great for murine xenografts, but I really do not know how to predict with other cell lines. I think every experiment demand a pilot study to assessits feasibility.
Dear Austin Morrissey
Although cancer cell lines are the most widely used starting material as they are readily available and propagated to provide sufficient material for in vitro manipulation and in vivo tumor growth, most of them have been established long time ago and have been selected and cultured under non-physiological conditions.
Whilst they serve as useful tools, there are significant limitations. This is because continual passage of these cell lines is accompanied by extensive clonal selection and consequent loss of heterogeneity. Moreover, different isolates of the same cell line can differ from one another at both the genomic and gene expression levels. Their lack of predictive value is highlighted by the absence of correlation between clinical results and in vitro and in vivo data obtained with cell lines, in part contributing to the >90% failure rate for the development of new oncology drugs.
In contrast, the least manipulated samples are those directly obtained from patients through surgical procedures or needle biopsies. However, one of the major challenges of using primary patient tumors is their limited shelf-life and very low quantity in most cases. Compared with cell line models and patient tissues, patient-derived xenografts (PDXs) provide a practical solution by both preserving the fidelity of clinical characteristics and providing tumor supply sufficient for most target identification and validation strategies.
Another significant benefit of using PDX for target identification and validation is that the process from target identification to validation and then to efficacy screening can be streamlined around the same models, therefore, offering a complete circle from patient to mouse and then back to patient.
Accumulating evidence has indicated that PDX models are superior to traditional cell line xenograft models because they maintain more similarities to the tumors found in actual patients. For example, if you do a detailed cytogenetic analysis of PDX models, it has been revealed that there is a strong preservation of the chromosomal architecture observed in patients. Furthermore, other studies have shown strong fidelity in histology, transcriptome, polymorphism and copy number variations.
So, I would rather use, human tumor samples cultured as cell lines to be implanted into mouse models.
Best.
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