Imaging spontaneous tumorigenesis: Inflammation precedes development of peripheral NK tumors

Dan Rauch, Shimon Gross, John Harding, Stefan Niewiesk, Michael Dale Lairmore, David Piwnica-Worms, Lee Ratner

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 intraepi-thelial 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 initiatesa 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.

Original languageEnglish (US)
Pages (from-to)1493-1500
Number of pages8
JournalBlood
Volume113
Issue number7
DOIs
StatePublished - Feb 12 2009
Externally publishedYes

Fingerprint

Taxation
Tumors
T-cells
Carcinogenesis
Deltaretrovirus
Inflammation
Imaging techniques
Natural Killer T-Cells
Luciferases
Lymphoma
Neoplasms
Granzymes
Adult T Cell Leukemia Lymphoma
Genetically Modified Animals
Trans-Activators
Terminal Repeat Sequences
Viruses
Oncogenes
Chemical activation
Animal Models

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Rauch, D., Gross, S., Harding, J., Niewiesk, S., Lairmore, M. D., Piwnica-Worms, D., & Ratner, L. (2009). Imaging spontaneous tumorigenesis: Inflammation precedes development of peripheral NK tumors. Blood, 113(7), 1493-1500. https://doi.org/10.1182/blood-2008-07-166462

Imaging spontaneous tumorigenesis : Inflammation precedes development of peripheral NK tumors. / Rauch, Dan; Gross, Shimon; Harding, John; Niewiesk, Stefan; Lairmore, Michael Dale; Piwnica-Worms, David; Ratner, Lee.

In: Blood, Vol. 113, No. 7, 12.02.2009, p. 1493-1500.

Research output: Contribution to journalArticle

Rauch, D, Gross, S, Harding, J, Niewiesk, S, Lairmore, MD, Piwnica-Worms, D & Ratner, L 2009, 'Imaging spontaneous tumorigenesis: Inflammation precedes development of peripheral NK tumors', Blood, vol. 113, no. 7, pp. 1493-1500. https://doi.org/10.1182/blood-2008-07-166462
Rauch, Dan ; Gross, Shimon ; Harding, John ; Niewiesk, Stefan ; Lairmore, Michael Dale ; Piwnica-Worms, David ; Ratner, Lee. / Imaging spontaneous tumorigenesis : Inflammation precedes development of peripheral NK tumors. In: Blood. 2009 ; Vol. 113, No. 7. pp. 1493-1500.
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