Lysyl oxidase propeptide (LOX-PP) inhibits oral cancer metastasis and tumor growth by interacting with stromal cell-derived factor 1 (SDF-1), syndecan-4 (SDC-4) and syndecan-1 (SDC-1)
10th Dentists and Prosthodontics Annual Meeting
June 27-28, 2016 New Orleans Louisiana, USA

Gokhan Baris Ozdener

Boston University, USA

Posters & Accepted Abstracts: Oral Health Dent Manag

Abstract:

The lysyl oxidase propeptide (LOX-PP) is derived from pro-lysyl oxidase (Pro-LOX) by extracellular biosynthetic proteolysis. LOX-PP inhibits oral cancer xenograft tumor growth and metastasis. Data indicate that LOX-PP inhibits distant metastasis of UMSCC2 oral carcinoma tumor xenograft by inhibiting shedding of SDC-1 and -4 ectodomains via down-regulating Stromal cell-derived factor 1 (SDF-1) activity. LOX-PP also binds both SDC1 and -4 and inhibits binding of FGFR1 to its ligand and the downstream signaling in non-metastatic oral cancer line SCC9. LOX-PP binds to SDC4 and inhibits SDC-4 oligomerization and FGFR1/FGF2/SDC-4 complex formation via SDC-4 to FGF2 binding in SCC9 cell line. We demonstrated that, LOX-PP promotes the formation of SDC-4/synectin/RhoGDI1/RhoG complex/ monomer. Therefore, dissociation of RhoG from RhoGDI1 is suppressed and eventually Rac-1 activation and cell proliferation inhibited in SCC9 cells. We also demonstrate that the uptake for LOX-PP is SDC-4 dependent macro-pinocytosis and SDC-1 regulates uptake/recycling of LOX-PP in both UMSCC2 and SCC9 cell lines.

Biography :

Email: ozzbaris@gmail.com