Lysyl oxidase oxidizes basic fibroblast growth factor and inactivates its mitogenic potential

Area of Science:

• Biochemistry
• Cell Biology
• Extracellular Matrix Biology

Background:

• Lysyl oxidase (LO) is crucial for extracellular matrix crosslinking.
• Basic fibroblast growth factor (bFGF) regulates cell proliferation, differentiation, and migration.

Purpose of the Study:

• To investigate the interaction between LO and bFGF.
• To determine how LO-mediated oxidation of bFGF affects its biological functions and cell growth.

Main Methods:

• Enzymatic oxidation of bFGF by LO.
• Analysis of bFGF crosslinking and oligomerization.
• Assessment of bFGF's mitogenic potential and nuclear localization in Swiss 3T3 cells.
• Evaluation of LO's effect on NIH 3T3 IgBNM 6-1 cell proliferation.

Main Results:

• LO oxidizes lysine residues in bFGF, leading to covalent crosslinking and formation of dimers and higher-order oligomers.
• Oxidized bFGF exhibits significantly reduced mitogenic potential and nuclear localization in Swiss 3T3 cells.
• Exposure of bFGF-overexpressing NIH 3T3 IgBNM 6-1 cells to LO markedly reduces their proliferative rates.
• LO activity correlates with suppressed ras-induced tumorigenesis and reduced cell growth.

Conclusions:

• LO directly modifies bFGF, altering its function and inhibiting cell proliferation.
• LO acts as a suppressor of both normal and transformed cell growth, potentially through bFGF modification.
• This study reveals a novel mechanism for LO in regulating cell growth and tumorigenesis.