Aberrant Collagen Cross-linking in Human Oral Squamous Cell Carcinoma

Journal of Dental Research
Tomoaki SaitoM Yamauchi

Abstract

Tumor progression is a complex process involving extracellular matrix (ECM) remodeling and stiffening. However, the mechanisms that govern these processes and their roles in tumor progression are still poorly understood. In this study, we performed bioinformatics, immunohistochemical, and biochemical analyses to examine if collagen cross-linking is associated with tumor stage and regional lymph node metastasis (RLNM) in oral squamous cell carcinoma (OSCC). We found that the genes encoding key enzymes for cross-linking are frequently overexpressed in oral, head, and neck cancers. Specifically, the enzymes lysyl hydroxylase 2 (LH2) or lysyl oxidase (LOX) and LOX-like 2 (LOXL2) were significantly upregulated in late-stage tumors and associated with poor patient prognosis. The protein levels of these enzymes in the primary human OSCC were also significantly increased in late-stage tumors and markedly elevated in the RLNM-positive tumors. Notably, while overall LOX/LOXL2-catalyzed collagen cross-links were enriched in late-stage and RLNM-positive tumors, LH2-mediated stable cross-links were significantly increased. To our knowledge, this is the first study to investigate the association of collagen cross-linking and expression of ke...Continue Reading

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Citations

Sep 30, 2020·Biochemical and Biophysical Research Communications·Hiroyuki YamaguchiYoshihiro Komatsu
Nov 14, 2020·Journal of Nanoscience and Nanotechnology·Tongwu WangDong Liang
Jun 10, 2021·Neoplasia : an International Journal for Oncology Research·Kotaro SatoAntonio L Amelio

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Methods Mentioned

BETA
RNAseq
surgical resections

Software Mentioned

OncoPrint
cBioPortal
Prism GraphPad
FireBrowse
GISTIC2
GISTIC
GraphPad

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