Stem Cells and Cancer
Rebecca J. Morris, Ph.D.

The Hormel Institute - Rebecca Morris
Human non-melanoma skin cancers (NMSCs) occur more frequently than any other malignancy, and approximately 1 million new cases are diagnosed in the United States annually, with a heavy burden on society. An estimated one-third to one-half of all human cancers originate in the skin, and skin cancers exceed all others combined. In the United States, the lifetime risk of skin cancer is 1 in 5. Solar ultraviolet radiation (UV) is the major known cause of NMSCs and is directly relevant to the etiology as demonstrated by epidemiological evidence and the tight correlation between NMSC in humans and UV-induced skin carcinogenesis in murine models. These cancers progress through an orderly sequence in which genetic, biochemical, and cellular abnormalities accumulate in target cells over time. Mild alterations initially seen within keratinocytes only can be identified histologically. Increased cellular atypia occurs with further sun damage, and then the development of hyperkeratotic, pre-malignant actinic keratoses. Of these, 1 to 10 percent will progress to squamous cell carcinomas (SCCs). Given that avoiding sunlight exposure is more easily said than done, the Morris laboratory is focusing on two specific projects.

The first project is related to the interactions between cutaneous epithelial cells and bone marrow cells. We are employing both in vitro models of co-culture and migration as well as in vivo models, using transplantation of genetically labeled bone marrow. Although these experiments remain in progress, we have found evidence of a dynamic interaction between the epidermis and bone marrow-derived cells in vitro and in vivo. We now are working on the mechanism of these interactions as well as the identification and isolation of the involved cells.

“Ultimately, these findings may provide potential targets for
treatment of non-melanoma skin cancers.””
Dr. Rebecca J. Morris

In the second project, we are working to identify novel keratinocyte stem cell regulatory genes. Keratinocyte stem cells have an unquestioned role in maintaining the normal structure and function of the epidermis and hair follicles, and they are thought to be important players in inherited and acquired skin diseases. Hence, identification of genes regulating their number and proliferative potential is a critical problem in cutaneous biology. To address this problem, we proposed a novel strategy for identifying genes involved in keratinocyte stem cell regulation. We made the surprising discovery that an innate immunity gene might play a role in regulating hair follicle stem cells. We now are working toward defining the mechanism and determining whether other genes are involved similarly.

The Hormel Institute - Rebecca Morris Lab

(Left to right) Kelsey Boland, Mi Sung Kim, Rebecca Morris, Yong Li, Taylor Picha
Not pictured: Kelly Johnson

In summary, research in the Morris laboratory continues to highlight the role of hair follicle stem cells in the pathogenesis of non-melanoma skin cancer, and has documented an unexpected contribution of bone marrowderived cells. Going forward, we will probe the interactions between epidermal stem cells and bone marrow-derived cells as tumor-initiating and propagating cells.