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