Loss of integrin α3 prevents skin tumor formation by promoting epidermal turnover and depletion of slow-cycling cells
| Autor: | Arnoud Sonnenberg, Norman Sachs, Laura van Hulst, Pablo Secades, Ji-Ying Song, Maaike Kreft |
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| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
Pathology medicine.medical_specialty Skin Neoplasms Integrin alpha3 9 10-Dimethyl-1 2-benzanthracene Cellular differentiation DMBA Tumor initiation Biology medicine.disease_cause Mice Cell Movement Cell Adhesion medicine Animals Cell Lineage Cell Proliferation Mice Knockout Multidisciplinary Staining and Labeling integumentary system Epidermis (botany) Keratin-15 Cell growth Cell Cycle Cell Differentiation Biological Sciences Cell cycle Hair follicle Mice Inbred C57BL Cell Transformation Neoplastic medicine.anatomical_structure Disease Progression Cancer research Epidermis Carcinogenesis Hair Follicle |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:21468-21473 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Progression through the various stages of skin tumorigenesis is correlated with an altered expression of the integrin α3β1, suggesting that it plays an important role in the tumorigenic process. Using epidermis-specific Itga3 KO mice subjected to the 7,12-dimethylbenzanthracene (DMBA)/12- O -tetradecanoylphorbol-13-acetate two-stage skin carcinogenesis protocol, we demonstrate that efficient tumor development is critically dependent on the presence of α3β1. In the absence of α3β1, tumor initiation is dramatically decreased because of increased epidermal turnover, leading to a loss of DMBA-initiated label-retaining keratinocytes. Lineage tracing revealed emigration of α3-deficient keratinocytes residing in the bulge of the hair follicle toward the interfollicular epidermis. Furthermore, tumor growth and cell proliferation were strongly reduced in mice with an epidermis-specific deletion of Itga3 . However, the rate of progression of α3β1-null squamous cell carcinomas to undifferentiated, invasive carcinomas was increased. Therefore, α3β1 critically affects skin carcinogenesis with opposing effects early and late in tumorigenesis. |
| Databáze: | OpenAIRE |
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