The dysfunction of BP180/collagen XVII in keratinocytes promotes melanoma progression.

Autor: Hwang BJ; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zhang Y; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Dermatology, School of Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an, China., Brozowski JM; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medicine-Rheumatology and Immunology, School of Medicine, Duke University, Durham, NC, USA., Liu Z; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Guangdong Center for Adverse Drug Reactions of Monitoring, Guangzhou, China., Burette S; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lough K; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Smith CC; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Shan Y; Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Chen J; Department of Dermatology, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Li N; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Williams S; Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Su M; Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Googe P; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Thomas NE; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Liu Z; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zhi_liu@med.unc.edu.; Department of Dermatology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zhi_liu@med.unc.edu.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zhi_liu@med.unc.edu.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2019 Dec; Vol. 38 (50), pp. 7491-7503. Date of Electronic Publication: 2019 Aug 21.
DOI: 10.1038/s41388-019-0961-9
Abstrakt: BP180, also termed collagen XVII, is a hemidesmosomal transmembrane glycoprotein expressed in basal keratinocytes, and functions as a cell-matrix adhesion molecule in the dermal-epidermal junction of the skin. Its function, other than cell-matrix adhesion, remains unclear. We generated a mouse strain with BP180 dysfunction (termed ∆NC16A), which develops spontaneous skin inflammation accompanied by an influx of myeloid derived suppressor cells (MDSCs). We used the B16 mouse melanoma model to demonstrate that BP180 dysfunction in either skin or basal keratinocytes promotes MDSC influx into skin and tumor progression. MDSC depletion reduced tumor progression in ∆NC16A mice, demonstrating a critical role for BP180 dysfunction-driven MDSCs in melanoma progression. This study provides the first direct evidence that BP180, a cell-cell matrix adhesion molecule, possesses antitumor function through modulating infiltration of MDSCs. Basal keratinocytes actively participate in skin microenvironment changes caused by BP180 dysfunction. ∆NC16A mice could be a new animal model to study the melanoma microenvironment.
Databáze: MEDLINE