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Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone

Gallas, Alyssa L
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954

Abstract Details

2014, MS, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Metastasis is the process by which a tumor migrates from its original position and travels to a distant location in the body through the bloodstream. It is a highly intricate process and accounts for 90% of all cancer deaths. This process can be studied through the use of the TGFΒRII conditional knockout mouse. In this mouse, expression of transforming growth factor Β receptor II (TGFΒRII) is conditionally lost in Keratin 14+ cells of stratified squamous epithelium, which results in the formation of a spontaneous tumor in the anorectal transition zone as well as in the lungs; those cells deficient in TGFΒRII permanently express the yellow fluorescent protein (YFP). We also induced a tumor by injecting YFP+ TGFΒRII-deficient tumor-propagating cells that were sorted from a separate tumor into the anorectal transition zone of a syngeneic recipient mouse. Similarly, TGFΒRII-deficient mice developing the spontaneous tumor and recipient mice with the induced tumor have YFP+ squamous cell carcinoma in their lungs. It was unknown whether the tumor in the lung of the spontaneous model formed as a result of metastasis or if it formed as a separate tumor from resident TGFΒRII-deficient Keratin 14+ cells of the trachea. To test this, we first looked at the trachea of the TGFΒRII conditional knockout mouse and found expression of Keratin 5 but not YFP, indicating that our knockout strategy is not active in the trachea. We then looked at various markers in the lungs to show that the lung tumor expresses the same markers of the spontaneous tumors but not the lung epithelia. We showed that the lung tumors express Keratin 5, Keratin 6 and Keratin 17, which are all coexpressed with the YFP+ tumor cells in both the spontaneous and induced tumors. We also showed that the lung marker thyroid transcription factor 1 (TTF1) is expressed around the tumor cells but does not coexpress with YFP. These data suggest that the tumor that forms in the lung is the result of a metastasis from the tumor in the anorectal transition zone. Further investigation into how this metastasis forms would potentially lead to the development of targeting strategies and better treatment options.
Geraldine Guasch, Ph.D. (Committee Chair)
Tatiana Kalin, M.D.Ph.D. (Committee Member)
Timothy Lecras, Ph.D. (Committee Member)
21 p.
Developmental Biology
TGFBeta; metastasis; transition zones; squamous cell carcinoma

Recommended Citations

Citations

  • Gallas, A. L. (2014). Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954

    APA Style (7th edition)

  • Gallas, Alyssa. Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone. 2014. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954.

    MLA Style (8th edition)

  • Gallas, Alyssa. "Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone." Master's thesis, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954

    Chicago Manual of Style (17th edition)

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