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TGFβ Receptor I Conditional Knockout Mice Develop Spontaneous Squamous Cell Carcinoma

Yasuyuki Honjo, Yansong Bian, Koji Kawakam, Alfredo Molinolo, Glenn Longenecker, Ramanamurthy Boppana, Jonas Larsson, Stefan Karlsson, J. Silvio Gutkind, Raj K. Puri and Ashok B. Kulkarni

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We generated a mouse model with a conditional deletion of TGF-β signaling in the neurons by crossing TGF-β receptor I (TβRI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity. To determine whether evasion of the immune response plays any role in this tumorigenesis, we analyzed the expression levels of receptors for interleukin-13 (mIL-13R), a key negative regulator of tumor immunosurveillance, and found that 33% of COKO tumors expressed the IL-13Rα2 chain. Primary cultures of the SCCs expressing IL-13Rα2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of TβRI can lead to spontaneous tumor formation. These mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and effect of anti-cancer therapeutics.

Authors

Yasuyuki Honjo

National Institutes of Health, Bethesda, Maryland

Yansong Bian

The Johns Hopkins Medical Institutions, Baltimore, MD

Koji Kawakam

Food and Drug Administration, Bethesda, Maryland

Alfredo Molinolo

National Institutes of Health; Bethesda, MD

Glenn Longenecker

National Institutes of Health, Bethesda, Maryland

Ramanamurthy Boppana

National Institutes of Health, Bethesda, Maryland

Jonas Larsson

Lund University Hospital, Lund, Sweden

Stefan Karlsson

Lund University Hospital, Lund, Sweden

J. Silvio Gutkind

National Institutes of Health, Bethesda, Maryland

Raj K. Puri

Food and Drug Administration, Bethesda, Maryland

Ashok B. Kulkarni

National Institutes of Health; Bethesda, MD

Purchase article for $19

Subscribe to this journal for $129/year