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

Bibliographic Details
Main Author: Gallas, Alyssa L.
Language:English
Published: University of Cincinnati / OhioLINK 2014
Subjects:
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin14068089542021-08-03T06:26:29Z 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. Developmental Biology TGFBeta metastasis transition zones squamous cell carcinoma 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. 2014-10-13 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Developmental Biology
TGFBeta
metastasis
transition zones
squamous cell carcinoma
spellingShingle Developmental Biology
TGFBeta
metastasis
transition zones
squamous cell carcinoma
Gallas, Alyssa L.
Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
author Gallas, Alyssa L.
author_facet Gallas, Alyssa L.
author_sort Gallas, Alyssa L.
title Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
title_short Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
title_full Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
title_fullStr Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
title_full_unstemmed Lung tumors formed in the TGFΒRII conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
title_sort lung tumors formed in the tgfβrii conditional knockout mouse are the result of metastasis from the spontaneous tumor in the anorectal transition zone
publisher University of Cincinnati / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406808954
work_keys_str_mv AT gallasalyssal lungtumorsformedinthetgfbriiconditionalknockoutmousearetheresultofmetastasisfromthespontaneoustumorintheanorectaltransitionzone
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