Lamin A and Prelamin A Counteract Migration of Osteosarcoma Cells

Evangelisti, Camilla; Paganelli, Francesca; Giuntini, Gaia; Mattioli, Elisabetta; Cappellini, Alessandra; Ramazzotti, Giulia; Faenza, Irene; Maltarello, Maria Cristina; Martelli, Alberto M.; Scotlandi, Katia; Chiarini, Francesca; Lattanzi, Giovanna

doi:10.3390/cells9030774

Cited by 17 publications

(11 citation statements)

References 53 publications

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“…In support of this, our previous work demonstrates that within osteosarcoma specimens Lamin A/C varies greatly and in dependance on cancer cell aggressiveness (Urciuoli et al, 2020). In support of our work, Evangelisti et al (2020) have confirmed that the condition of low Lamin A expression confers to osteosarcoma cells a significant increase in migration potential, while overexpression of Lamin A reduces their migration ability. Here, we deepened Lamin A/C involvement in osteosarcoma cell tumoral behavior, showing that its reintegration in high metastatic 143B cells, expressing basal low levels of Lamin A/C, restores cell adhesion properties as well as tumor features of low aggressive nonmetastatic osteosarcoma cells.…”

Section: Discussionsupporting

confidence: 88%

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

Urciuoli

D’Oria

Petrini

et al. 2021

Front. Cell Dev. Biol.

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Besides its structural properties in the nucleoskeleton, Lamin A/C is a mechanosensor protein involved in perceiving the elasticity of the extracellular matrix. In this study we provide evidence about Lamin A/C-mediated regulation of osteosarcoma cell adhesion and spreading on substrates with tissue-specific elasticities. Our working hypothesis is based on the observation that low-aggressive and bone-resident SaOS-2 osteosarcoma cells express high level of Lamin A/C in comparison to highly metastatic, preferentially to the lung, osteosarcoma 143B cells, thereby suggesting a role for Lamin A/C in tumor cell tropism. Specifically, LMNA gene over-expression in 143B cells induced a reduction in tumor cell aggressiveness in comparison to parental cells, with decreased proliferation rate and reduced migration capability. Furthermore, LMNA reintegration into 143B cells changed the adhesion properties of tumor cells, from a preferential tropism toward the 1.5 kPa PDMS substrate (resembling normal lung parenchyma) to the 28 kPa (resembling pre-mineralized bone osteoid matrix). Our study suggests that Lamin A/C expression could be involved in the organ tropism of tumor cells, thereby providing a rationale for further studies focused on the definition of cancer mechanism of metastatization.

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Section: Discussionsupporting

confidence: 88%

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

Urciuoli

D’Oria

Petrini

et al. 2021

Front. Cell Dev. Biol.

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“…The aberrant expression of Lamin A/C has been reported in a variety of cancer types with ambivalent roles in tumour progression [13]. Its decreased expression in breast, prostate, colon, ovarian, gastric, and endometrial cancer and osteosarcoma correlated with a reduction in overall patient survival and an increase in metastasis and tumour relapse [15,[28][29][30]. In agreement with these works, in previous papers we also found that LMNA expression was related to a less malignant phenotype in human neuroblastoma [23,26].…”

Section: Discussionsupporting

confidence: 86%

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

et al. 2021

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Nuclear lamina components have long been regarded as scaffolding proteins, forming a dense fibrillar structure necessary for the maintenance of the nucleus shape in all the animal kingdom. More recently, mutations, aberrant localisation and deregulation of these proteins have been linked to several diseases, including cancer. Using publicly available data we found that the increased expression levels of the nuclear protein Lamin A/C correlate with a reduced overall survival in The Cancer Genome Atlas Research Network (TCGA) patients affected by glioblastoma multiforme (GBM). We show that the expression of the LMNA gene is linked to the enrichment of cancer-related pathways, particularly pathways related to cell adhesion and cell migration. Mimicking the modulation of LMNA in a GBM preclinical cancer model, we confirmed both in vitro and in vivo that the increased expression of LMNA is associated with an increased aggressiveness and tumorigenicity. In addition, delving into the possible mechanism behind LMNA-induced GBM aggressiveness and tumorigenicity, we found that the mTORC2 component, Rictor, plays a central role in mediating these effects.

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“…Previously, we have demonstrated that an impaired nuclear lamina, due to mutations of the gene encoding lamin A/C, i.e., LMNA , is responsible for an unusual nuclear recruitment of Ankrd2 even under basal conditions [ 18 ]. Of note, lamin A/C has been recently correlated with the migration potential of OS cells [ 19 ]. The subcellular localization of Ankd2 in the OS cell lines was next evaluated by immunofluorescence.…”

Section: Resultsmentioning

confidence: 99%

Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells

Piazzi

Kojić

Capanni

et al. 2021

Cancers

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Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in examining the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives.

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Lamin A and Prelamin A Counteract Migration of Osteosarcoma Cells

Cited by 17 publications

References 53 publications

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

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

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells

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