Page 50 - Hormel Report 2021

Rebecca Morris, Ph.D.
“Our research creates new knowledge
in epithelial stem cell biology and the
etiology of epithelial cancers.”
Rebecca Morris
50 | THE HORMEL INSTITUTE // Stem Cells and Cancer
SECTION LEADER / 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 cytokeratin expres- sion usually cover body surfaces (like epidermis) or line spaces (like the linings of the gastrointes- tinal and respiratory tracts). However, research has identified cytokeratin+/EpCAM+ bone mar- row derived epithelial cells in “normal, healthy” human subjects. To our knowledge, no one has performed functional analyses and characteriza- tion of these cells. This is a gap in our knowledge of epithelial 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 initi- ating cells. Moreover, the blood borne epithelial cells currently interfere with liquid biopsies as “contaminating” cells. We therefore hypothesize that bone marrow derived epithelial cells include a novel population of progenitors that can be