Functional Role of Specific Secreted and Cell Surface Molecules inc Tumour Cell Invasion and Metastasis

We have shown in a previous paper (Devl Biol. 135, 449, 1989) that axons regenerating from postnatal neurons are unable to penetrate three-dimensional cultures of mature astrocytes, while axons from embryonic dorsal root ganglia (DRGs) and retina will grow through such cultures for considerable distances. We have now investigated the role of proteases in the penetration of three-dimensional astrocyte cultures by axons from embryonic DRGs. Embryonic DRGs were grown in association with three-dimensional astrocyte cultures, with astrocyte monolayers, and with-air dried collagen. The effects of inhibitors of the three families of proteases that have been shown to be involved in tumour cell invasion were investigated. The serine protease inhibitors EACA and Trasylol both reduced growth in three-dimensional astrocyte cultures to around 50% of control, but had little effect on growth on astrocyte monolayers or on collagen. TIMP, which inhibits collagenases, had no effect on growth on two- or three-dimensional cultures. Cbz-gly-phen-amide, an inhibitor of enteroproteases, reduced growth in all three types of culture.

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Lacticaseibacillus rhamnosus GG inhibits infection of human keratinocytes by Staphylococcus aureus through mechanisms involving cell surface molecules and pH reduction

Beneficial Microbes ◽

10.3920/bm2020.0075 ◽

2020 ◽

pp. 1-14

Author(s):

I. Spacova ◽

C. O’Neill ◽

S. Lebeer

Keyword(s):

Staphylococcus Aureus ◽

Cell Surface ◽

Human Keratinocytes ◽

Additional Contribution ◽

Cell Surface Molecules ◽

Primary Human Keratinocytes ◽

Surface Molecules ◽

Additional Cell ◽

Competitive Adhesion

Beneficial bacteria represent an emerging tool against topical diseases, including infection caused by Staphylococcus aureus. Here, we investigated several anti-pathogenic mechanisms of the model probiotic Lacticaseibacillus rhamnosus GG against a clinical S. aureus isolate by implementing various mutants lacking important cell surface molecules. We analysed adhesion of L. rhamnosus and competitive adhesion with S. aureus to primary human keratinocytes, L. rhamnosus and S. aureus auto- and co-aggregation, S. aureus growth inhibition, keratinocyte viability increase, and monocyte Toll-like receptor (TLR) activation by L. rhamnosus as such, or with S. aureus. L. rhamnosus mutated in SpaCBA pili exhibited reduced adhesion to keratinocytes, reduced ability to prevent S. aureus adhesion to keratinocytes and reduced co-aggregation with S. aureus. Mutants in cell wall exopolysaccharides showed enhanced adhesion to keratinocytes and TLR activation in monocytes, suggesting involvement of additional cell surface molecules masked by exopolysaccharides. All L. rhamnosus strains inhibited S. aureus growth, likely due to acidification of the medium. Live (but not UV-inactivated) L. rhamnosus significantly reduced inflammatory TLR activation in monocytes by S. aureus. These data suggest the key role of SpaCBA pili and additional contribution of other cell surface molecules as well as secreted components of L. rhamnosus GG in the multifactorial inhibition of S. aureus adhesion and toxicity in the skin niche.

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