Imaging spontaneous tumorigenesis: inflammation precedes development of peripheral NK tumors

Abstract

Early events in tumor development are spontaneous, microscopic, and affected by the microenvironment. We developed a mouse model of spontaneous lymphoma in which malignant transformation is coupled with light emission that can be detected noninvasively using bioluminescent imaging. The human T-cell leukemia virus (HTLV) type 1 transcriptional transactivator Tax is an oncogene sufficient to produce lymphoma in transgenic animal models. Using the granzyme B promoter to restrict Tax expression to the mature natural killer (NK)/T-cell compartment, we have reproduced many elements of HTLV-associated adult T-cell leukemia/lymphoma. Tax activates signaling cascades associated with transformation, inflammation, and tumorigenesis. Here, we report that Tax-mediated activation of luciferase in long terminal repeat-luciferase (LTR-LUC) mice serves as a reporter for imaging these processes in vivo. Using bioluminescent imaging (BLI), we discovered that microscopic intraepithelial lesions precede the onset of peripheral subcutaneous tumors, tumorigenesis progresses through early reversible stages, and Tax is sufficient for inducing tumors. Based on these findings, we propose that Tax expression in activated lymphocytes initiates a cascade of events that leads to NK/T cell recruitment, activation, and transformation. The use of BLI expands our ability to interrogate the role of Tax in tumorigenesis in vivo and has made the association of inflammation with tumor initiation amenable for study.

Mechanisms of Nanoparticle-Mediated siRNA Transfection by Melittin-Derived Peptides

“…Transgenic mice with spontaneous tumors were a gift from the Ratner lab. 71 Mice with advanced tumors were selected for pilot experiments and injected with a single dose at 1mg/kg 24 hours before sacrifice. Animals were perfused with saline, and tumors were excised for IVIS imaging and frozen sectioning.…”

Opposing control by transcription factors MYB61 and MYB3 Increases Freezing Tolerance by relieving C-repeat Binding Factor suppression

“…Infiltrated plants were incubated at 22°C for 48 h before imaging with a digital CCD camera (Carestream In-vivo FX PRO;Rauch et al, 2009). A lowlight cooled CCD imaging apparatus was used to capture LUC images and determine the luminescence intensity.…”

Establishment of a bioluminescent imaging-based in vivo leukemia model by intra-bone marrow injection

“…Therefore, our rationale for IBMT approach to establish leukemia animal model was based on evidence that bone marrow microenvironment plays a significant role in promoting survival and proliferation of leukemic cells (22). A growing number of in vivo models for experimental therapeutics relevant to human cancers, such as hematological malignancies, are used in combination with a bioluminescent imaging system to trace leukemia progression in real-time and elucidate underlying biological mechanisms of leukemogenesis (23)(24)(25)(26)(27). Furthermore, the combination of bioluminescence and imaging has superseded previous invasive monitoring methods, including serial tail-vein PB sampling, as a more desirable alternative (28).…”