Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer.
angiolymphatic invasion (ALI)
collective cancer cell migration
discoidin domain receptor-1 (DDR1)
oral squamous cell carcinoma (OSCC)
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
31 Mar 2020
31 Mar 2020
Historique:
received:
29
02
2020
revised:
29
03
2020
accepted:
30
03
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
5
4
2020
Statut:
epublish
Résumé
The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Previously, we identified an elevated expression of DDR1 in oral squamous cell carcinoma (OSCC) cells. Through the data mining of a microarray dataset composed of matched tumor-normal tissues from forty OSCC patients, we distilled overexpressed genes statistically associated with angiolymphatic invasion, including DDR1, COL4A5, COL4A6 and PDPN. Dual immunohistochemical staining further confirmed the spatial locations of DDR1 and PDPN in OSCC tissues indicative of collective cancer cell invasion. An elevated DDR1 expression at both the transcription and protein level was observed by treating keratinocytes with collagen of fibrillar or basement membrane types. In addition, inhibition of DDR1 kinase activity in OSCC TW2.6 cells disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues. Taken together, these results suggest that collagen deposition in the affected tissues followed by DDR1 overexpression could be central to OSCC tumor growth and angiolymphatic invasion. Thus, DDR1 inhibitors are potential therapeutic compounds in restraining oral cancer, which has not been previously explored.
Identifiants
pubmed: 32244515
pii: cancers12040841
doi: 10.3390/cancers12040841
pmc: PMC7226486
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : National Health Research Institutes
ID : CA-108-PP-05
Organisme : Ministry of Science and Technology
ID : MOST 107-2314-B-400-029
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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