One of the most challenging questions in the study of cancer is the origin and the nature of the cells that initiate cancer. Accumulated studies have provided many molecular origins of cancers but we still do not know what kind of cells in the tissues transform to cancer cells. Therefore, identifying the cellular origin of these cells is critical for the development of better prognosis, diagnosis and treatment of cancer. A stem cell origin of cancer has been postulated over 150 years. Recent cancer stem cell studies have opened a new window on aspects of the cellular origin of cancer.
In this communication, we will address two possible cellular origins of cancer in epithelial tumor development using mouse skin cancer model: tissue specific stem cells, and cells from other organs. To demonstrate contribution of the tissue specific stem cells in tumor development, we monitored the contribution of keratin-15 positive hair follicle bulge stem cells to skin tumor development in the multistage skin carcinogenesis model with Krtl- 15CrePRl;R26R transgenic mice. We found that labeled progeny of the keratin-15 positive bulge stem cells migrate into papillomas and these cells contribute to almost all papilloma samples by 20 weeks of promotion. Additionally, in contrast to the transient contribution of bulge-derived cells in skin wound healing, consistent percentage of the bulge-derived cells stay in the papillomas over 20 weeks.
Furthermore, papillomas have heterogeneous expression of the codon 61 signature Ha-ras mutation, with approximately 30 percent of bulge-derived regions expressing the mutation. To determine the contribution of exogenous sources in skin tumor development, we examined bone marrow-derived cells (BMDCs) in the skin tumors from the allogeneic gender-mismatched bone marrow transplantation recipient mice after chemical skin carcinogenesis. We observed that genetically marked (EGFP) BMDCs were detected in the epithelial part of skin wounds and also skin tumors, and we found greater degree of BMDC contribution in chronic ulcer-related skin lesions. Lastly, an in-vitro assay demonstrated plasticity of BMDCs by inducing keratin-14 expressing cells from mesenchymal stem cells. These results demonstrated that hair follicle bulge stem cells and also BMDCs are able to contribute to skin tumor development.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/yn5c-0r94 |
| Creators | Park, Heuijoon |
| Source Sets | Columbia University |
| Detected Language | English |
| Type | Theses |
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