Lumican affects actin cytoskeletal organization in human melanoma A375 cells

Radwańska, Agata; Baczyńska, Dagmara; Nowak, Dorota; Brézillon, Stéphane; Popow, Agnieszka; Maquart, François‐Xavier; Wegrowski, Yanusz; Malicka-Błaszkiewicz, Maria

doi:10.1016/j.lfs.2008.09.008

Cited by 29 publications

(33 citation statements)

References 65 publications

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“…The consistency of effects in vivo highlights the importance of the host microenvironment in cancer progression. Earlier reports have demonstrated that lumican consistently has a negative effect on melanoma cells in vitro, making it difficult to fully appreciate or isolate the in vivo effects of lumican on the host microenvironment [15,17,35]. Additionally, our previous findings suggested that lumican's anti-angiogenic potential could be implicated in the reduced tumor volume [21].…”

Section: Discussionmentioning

confidence: 87%

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

Williams

Fulford

Albig

2010

Cancer Microenvironment

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Matrikines are important components of tumor microenvironments that integrate communication between extracellular matricies and membrane-bound receptors thereby regulating cellular behaviors. One such matrikine that is differentially expressed in cancer microenvironments is the extracellular matrix protein lumican; however its precise role in cancer remains ambiguous. To study the effects of lumican on cancer cells, we created lumican-overexpressing cell lines from murine fibrosarcoma (MCA102) and pancreatic adenocarcinoma (Pan02) cells. Lumican overexpression in Pan02 cells increased invasiveness, decreased soft agar colony size, and increased proliferation. Conversely in MCA102 cells, lumican decreased invasiveness, increased soft agar colony size, but did not influence proliferation. In contrast to these pleiotropic in vitro results, lumican overexpression within the in vivo tumor microenvironment produced uniformly smaller tumors. Importantly, reduced tumor size was correlated with reduced vascular density. Consistent with lumican's proposed anti-angiogenic activity, lumican increased endothelial cell apoptosis. Importantly, lumican was previously shown to influence Fas expression and our results show that lumican enhanced Fas mediated endothelial cell apoptosis although we were unable to detect any difference in Fas or Fas ligand expression between lumican-overexpressing and control cells. Interestingly, lumican had no effect on MCA102 apoptosis, suggesting that the observed reduction in tumor size is specifically due to endothelial cell apoptosis rather than a direct effect on the cancerous cells themselves. Therefore, this study is the first to demonstrate a causal relationship between tumor reduction and lumican's effect on angiogenesis as opposed to an effect on the cancerous cells themselves.

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Section: Discussionmentioning

confidence: 87%

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

Williams

Fulford

Albig

2010

Cancer Microenvironment

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“…Our previous work indicates that lumican affects morphology and actin cytoskeletal organization of human melanoma A375 cells [20]. It was also shown that lumican core protein induces an alteration of the link between actin filaments and a2b1 integrin, which leads to destabilization of focal adhesion complexes and a decrease in melanoma A375 cells migration ability [21,22].…”

Section: Discussionmentioning

confidence: 91%

“…It was previously observed that lumican core affects actin cytoskeletal organization and contributes to melanoma A375 cell migration, through binding with a2b1 integrin [20,21]. In presence of lumican cytosolic accumulation of vinculin, one of the focal adhesion proteins was observed [21,22].…”

Section: Introductionmentioning

confidence: 81%

Overexpression of lumican affects the migration of human colon cancer cells through up-regulation of gelsolin and filamentous actin reorganization

Radwańska

Litwin

Nowak

et al. 2012

Experimental Cell Research

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“…No significant difference in β1 integrin expression (130 kDa and 120 kDa bands) could be observed in presence or in absence of lumican in MSC. In EPC, the β1 integrin expression was slightly increased in presence of lumican The distribution of actin cytoskeleton, which is altered in melanoma cells in presence of lumican [25], was not significantly remodelled in MSC and EPC in comparison to other ECM substrata (supplemental material, Figure S1). Moreover, we investigated by Western immunoblotting (supplemental material, Figure S2) the ratio of FAK-pY397 to total FAK in MSC and EPC incubated for 15 min with or without 100 nM lumican.…”

Section: Resultsmentioning

confidence: 96%

Effect of Lumican on the Migration of Human Mesenchymal Stem Cells and Endothelial Progenitor Cells: Involvement of Matrix Metalloproteinase-14

et al. 2012

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BackgroundIncreasing number of evidence shows that soluble factors and extracellular matrix (ECM) components provide an optimal microenvironment controlling human bone marrow mesenchymal stem cell (MSC) functions. Successful in vivo administration of stem cells lies in their ability to migrate through ECM barriers and to differentiate along tissue-specific lineages, including endothelium. Lumican, a protein of the small leucine-rich proteoglycan (SLRP) family, was shown to impede cell migration and angiogenesis. The aim of the present study was to analyze the role of lumican in the control of MSC migration and transition to functional endothelial progenitor cell (EPC).Methodology/Principal FindingsLumican inhibited tube-like structures formation on Matrigel® by MSC, but not EPC. Since matrix metalloproteinases (MMPs), in particular MMP-14, play an important role in remodelling of ECM and enhancing cell migration, their expression and activity were investigated in the cells grown on different ECM substrata. Lumican down-regulated the MMP-14 expression and activity in MSC, but not in EPC. Lumican inhibited MSC, but not EPC migration and invasion. The inhibition of MSC migration and invasion by lumican was reversed by MMP-14 overexpression.Conclusion/SignificanceAltogether, our results suggest that lumican inhibits MSC tube-like structure formation and migration via mechanisms that involve a decrease of MMP-14 expression and activity.

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Lumican affects actin cytoskeletal organization in human melanoma A375 cells

Cited by 29 publications

References 65 publications

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

Lumican Reduces Tumor Growth Via Induction of Fas-Mediated Endothelial Cell Apoptosis

Overexpression of lumican affects the migration of human colon cancer cells through up-regulation of gelsolin and filamentous actin reorganization

Effect of Lumican on the Migration of Human Mesenchymal Stem Cells and Endothelial Progenitor Cells: Involvement of Matrix Metalloproteinase-14

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