Page 48 - Hormel Institute Annual Report 2021-22
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 Rebecca Morris, PhD
 “Our research creates new knowledge
in epithelial stem cell biology and the
etiology of epithelial cancers.”
Rebecca Morris
48 | THE HORMEL INSTITUTE Stem Cells and Cancer
PROFESSOR
// UNIVERSITY OF MINNESOTA
Tantalizing evidence has supported the existence of epithelial cells in blood and bone marrow since the advent of reverse
transcription polymerase chain reaction. First discovered in patients with breast and prostate cancer, these circulating epithelial cells were quickly identified as metastatic epithelial cells. Perplexingly, however, traces of cytokeratin mRNAs were also found in the blood and bone marrow of many normal volunteers. These were dismissed as artifacts, or metastases from an occult tumor, or in some cases, circulating fetal cells. Nevertheless, observations of blood borne epithelial cells persisted over time in both human and murine subjects. Our interest in these rare circulating epithelial cells was ignited by our recently published data demonstrating that, in
in vivo, cells of bone marrow origin are recruited to chronically hyperplastic epidermis and devel- oping cutaneous neoplasms where they became as epidermal cells. They produced epidermal cytokeratins, proliferated, differentiated, des- quamated, and persisted as epithelial cells over many months, still maintaining the green fluores- cent protein or the Y-chromosome of their bone marrow origin. Although there are several expla- nations for this requiring further experimentation, we were reminded of the rtPCR control subjects leading us to hypothesize that the recruited
keratinocytes were bone marrow derived epithelial progenitor cells seeking a niche. To this end, we are currently pursuing two projects.
Epithelial cells identified by cytoker- atin expression usually cover body surfaces (like epidermis) or line
spaces (like the linings of the gastrointestinal and respiratory tracts). However, research has identi- fied cytokeratin+/EpCAM+ bone marrow derived epithelial cells in “normal, healthy” human sub- jects. To our knowledge, no one has performed functional analyses and characterization of these cells. This is a gap in our knowledge of epithe-
lial biology with ramifications towards human health, particularly regarding conditions where hair follicle or epidermal stem cells have been damaged or destroyed; in instances of chronic inflammation; or in squamous cancers where we know they can function as tumor initiating cells. Moreover, the blood borne epithelial cells current- ly interfere with liquid biopsies as “contaminat- ing” cells. We therefore hypothesize that bone marrow derived epithelial cells include a novel population of progenitors that can be recruited to chronically compromised epithelium and regener- ate it. Our specific aims are to analyze these cells in vitro and in vivo using strategies that my labo- ratory and others have developed for identifying
        



















































































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