Mechanisms of Chemical Cooperative Carcinogenesis by Epidermal Langerhans Cells
| Autor: | Cynthia L. Kucher, Haihui Liao, Robert E. Tigelaar, Kseniya Golubets, Renata B. Filler, Peter Yu Cheng Zhao, Julia M. Lewis, Juliet A. Fraser, Michael Girardi, Christina D. Bürgler |
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| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
Pathology medicine.medical_specialty Skin Neoplasms Carcinogenesis 9 10-Dimethyl-1 2-benzanthracene CYP1B1 DMBA Dermatology Biology medicine.disease_cause Biochemistry Cell Line Malignant transformation Mice medicine Animals Neoplastic transformation Molecular Biology Cells Cultured Mice Knockout Epidermis (botany) Cell Biology 3. Good health Disease Models Animal Cell Transformation Neoplastic Tumor progression Cell culture Langerhans Cells Cytochrome P-450 CYP1B1 Carcinoma Squamous Cell Cancer research Mutagens |
| Zdroj: | Journal of Investigative Dermatology. 135(5):1405-1414 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2014.411 |
| Popis: | Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation. |
| Databáze: | OpenAIRE |
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