Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

Urciuoli, Enrica; D’Oria, Valentina; Petrini, Stefania; Peruzzi, Barbara

doi:10.3389/fcell.2021.712377

Cited by 17 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altered lamin A/C expression has been described in other orthopaedic pathological conditions, including cancer: in paediatric osteosarcoma, lamin A/C scales with tumour aggressiveness [33], and the restoration of lamin A/C expression in high aggressive osteosarcoma cells reduced cancer cell migration [34] and aggressiveness [35]. In view of this, our study shed light on the relevance of lamins and the mechanotransduction process in orthopaedic diseases, both in adult and paediatric patients.…”

Section: Discussionsupporting

confidence: 56%

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

Candela

Peruzzi

Leopizzi

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamina. A and B-type lamins are the major components of the nuclear lamina. Lamins have been associated with important cellular functions: DNA replication, chromatin organization, differentiation of the cell, apoptosis and in maintenance of nuclear structure. Little is known regarding the etiopathogenesis of adhesive capsulitis (AC); recently, a dysregulating fibrotic response starting from a subpopulation has been described within the fibroblast compartment that suddenly turns on an activated phenotype.Considering the key role of A-type lamin in the regulation of cellular stability and function we performed an immunohistochemical analysis to compare the lamin A/C expression between patients with AC and healthy controls.Materials and methods: Twenty-six patients [12M-14F, mean age (SD): 52.3 (6.08)] were enrolled. Tissue samples excised from the rotator interval were analysed for lamin A/C expression by immunohistochemistry. Controls were represented by samples obtained by normal rotator interval excised from patients submitted to shoulder surgery [6M-9F, mean age (SD): 57.1 (5.3)]. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed.Results: The expression of lamin A/C was found to be significantly lower in the fibroblasts of patients with adhesive capsulitis when compared to controls (intensity of staining: p: 0.005; H-score: 0.034); no differences were found regarding the synoviocytes (p>0.05). Considering only patients with AC, lamin A/C intensity staining was found to be significantly higher in samples where acute inflammatory infiltrate was detected (p: 0.004). No significant changes in levels of lamin A/C expression were documented between the mild and severe adhesive capsulitis severity groups.Conclusions: Our study demonstrated that the activity of lamin A/C in maintaining nuclear structural integrity and cell viability is decreased in patients with adhesive capsulitis. The timing of the pathogenetic process is the key factor for cell functionality which is maintained in the early stages of the disease; on the contrary, the clinical severity of adhesive capsulitis plays a marginal role on nuclear stability.Level of Evidence: III

show abstract

Section: Discussionsupporting

confidence: 56%

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

Candela

Peruzzi

Leopizzi

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Confocal microscopy was performed as described in Urciuoli et al . 18 Images are processed using Adobe Photoshop V.CS4 software (Adobe Systems Inc).…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56^brightCD16⁻subset

Veneziani

Alicata

Pelosi

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundToll-like receptors (TLRs) are pattern-recognition sensors mainly expressed in innate immune cells that directly recognize conserved pathogen structures (pathogen-associated molecular patterns-PAMPs). Natural killer (NK) cells have been described to express different endosomal TLRs triggered by RNA and DNA sequences derived from both viruses and bacteria. This study was addressed to establish which endosomal TLR could directly mediate NK activation and function after proper stimuli. It was also important to establish the most suitable TLR agonist to be used as adjuvant in tumor vaccines or in combined cancer immunotherapies.MethodsWe assessed endosomal TLR expression in total NK cells by using RT-qPCR and western blotting technique. In some experiments, we purified CD56brightCD16− and CD56dimCD16+ cells subsets by using NK Cell Isolation Kit Activation marker, cytokine production, CD107a expression and cytotoxicity assay were evaluated by flow cytometry. Cytokine release was quantified by ELISA. NK cells obtained from ovarian ascites underwent the same analyses.ResultsAlthough the four endosomal TLRs (TLR3, TLR7/8, and TLR9) were uniformly expressed on CD56brightCD16− and CD56dimCD16+ cell subsets, the TLR7/8 (R848), TLR3 (polyinosinic-polycytidylic acid, Poly I:C) and TLR9 (ODN2395) ligands promoted NK-cell function only in the presence of suboptimal doses of cytokines, including interleukin (IL)-2, IL-12, IL-15, and IL-18, produced in vivo by other environmental cells. We showed that R848 rather than TLR3 and TLR9 agonists primarily activated CD56brightCD16− NK cells by increasing their proliferation, cytokine production and cytotoxic activity. Moreover, we demonstrated that R848, which usually triggers TLR7 and TLR8 on dendritic cells, macrophages and neutrophils cells, activated CD56brightCD16− NK-cell subset only via TLR8. Indeed, specific TLR8 but not TLR7 agonists increased cytokine production and cytotoxic activity of CD56brightCD16− NK cells. Importantly, these activities were also observed in peritoneal NK cells from patients with metastatic ovarian carcinoma, prevalently belonging to the CD56brightCD16− subset.ConclusionThese data highlight the potential value of TLR8 in NK cells as a new target for immunotherapy in patients with cancer.

show abstract

“…Therefore, we check whether this is due to the impaired nuclear architecture that may affect nucleus function. The association between higher lamin B1 expression levels and nuclear dysmorphisms in OS cell lines has been already suggested [83] . Moreover, it has been shown that lamin A interacts with the m 6 A methyltransferases, METTL3 and METTL14 in nuclear speckles [84] .…”

Section: Resultsmentioning

confidence: 84%

RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines

Betlej¹,

Ząbek²,

Lewińska³

et al. 2022

Journal of Bone Oncology

View full text Add to dashboard Cite

Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

Cited by 17 publications

References 47 publications

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56^brightCD16⁻subset

RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines

Contact Info

Product

Resources

About

Lamin A/C Mechanosensor Drives Tumor Cell Aggressiveness and Adhesion on Substrates With Tissue-Specific Elasticity

Cited by 17 publications

References 47 publications

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

The effect of cellular nuclear function alteration on the pathogenesis of shoulder adhesive capsulitis. An immunohistochemical study on Lamin A/C expression

Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56brightCD16−subset

RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines

Contact Info

Product

Resources

About

Toll-like receptor 8 agonists improve NK-cell function primarily targeting CD56^brightCD16⁻subset