Propagating cell frequencies increase further after passage through the mice, most likely due to selection of clones better adapted to the murine microenvironment (Clappier et al, 2011).
Thanks to microsatellite analysis, we can rule out errors in tumor tracking and state positively that these differences reflect a genuine biological process, for example a selection of malignant cells more prone to grow in the murine microenvironment or a direct influence of this microenvironment on gene expression profile as reported in other models [ 16, 17].
Although it is formally possible to functionally assess single cancer cells for differences in proliferation, metastasis and therapy resistance in mouse xenograft studies, these experiments are cost-prohibitive and leave some questions as to whether transplant of a human cell into a murine microenvironment alters the true cellular function (Quintana et al., 2008).
It is also possible that unlicensed human NK cells become activated by cytokines present in the murine microenvironment.
Previous studies showed that intracavitary targeting of the murine microenvironment with a lentiviral vector expressing murine interferon-α1 (mIFN-α1) exerted a significant antineoplastic activity in a xenograft mouse model of PEL 25.
This indicates that these properties are modified neither by the xenotransplantation process nor by the murine microenvironment and likely depend on the particular genetic alterations present in the leukemic clone.
In the present study, we have achieved two goals: first, to establish a novel mouse model using NOG recipients engrafted with primary DLBCL cells from a patient, in which the tumor cells survive and proliferate in a murine microenvironment-dependent manner; second, to document that bevacizumab possesses significant therapeutic efficacy in these primary DLBCL cell-bearing mice.
In conclusion, using NOG mice as recipients, we have established a novel model in which primary DLBCL cells from a patient engraft and proliferate in a murine microenvironment-dependent manner.
To emphasize the importance and complexity of the microenvironment to cancers, we discuss how environmental factors, such as physical, chemical and biological factors, alter the microenvironment.
Hence, our MCL model creates a reasonable tumor microenvironment to study NP transport in tumor tissue.
