Effects of fibulin-5 on attachment, adhesion, and proliferation of primary human endothelial cells

Preis, Meir; Cohen, Tzafra; Sarnatzki, Y; Yosef, Y. Ben; Schneiderman, Jacob; Gluzman, Zoya; Koren, Belly; Lewis, Basil S.; Shaul, Yoav D.; Flugelman, Moshe Y.

doi:10.1016/j.bbrc.2006.07.156

Cited by 50 publications

(48 citation statements)

References 26 publications

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“…It is noteworthy that our experimental set-up using native collagen fascicles, a fibroblast cell line, and individual proteases may not completely mimic the complex natural action of collagenases in vivo during health and disease states. For example, excess activity of multiple interstitial collagenases could be correlated with a chronically nonhealing wound (44). Nevertheless, our results highlight another, previously unrecognized level of complexity, showing that each protease exhibits a unique proteolytic pattern within the native tissue.…”

Section: Discussionmentioning

confidence: 54%

“…For example, our data confirmed the previously reported MMP-13 specificity for the GP tenascin-C (41), and the PG aggrecan (42) and showed much broader specificity of MMP-13 to matrisome proteins. Other differentially released noncollagenous components include PGs such as decorin and fibromodulin and GPs such as fibulin 5, all known to be critical for cell signaling, spreading, and motility (43)(44)(45). Taken together, these data demonstrate that both collagenases effectively degrade native collagen-rich ECM in a highly selective mode which consequently releases bioactive matrisome molecules and at the same time exposes new matrix-associated epitopes and protein complexes.…”

Section: Mmp-1 and Mmp-13 Produce Distinct Microscale Morphologies Andmentioning

confidence: 82%

“…In addition, under physiological conditions the release or degradation of these matrisome molecules was reported to contribute to cell signaling through their interactions with cell-surface molecules (45,49,50). Finally, selective degradation of PGs and GPs is known to contribute to cell adhesion and activation of cell proliferation (43,44,51,52).…”

Section: Discussionmentioning

confidence: 99%

“…Overall, the remodeling events of collagenrich ECM by either MMP-1 or MMP-13 contributed to fibroblastmatrix communication, suggesting that such stimulation may be involved in cell migration in normal and pathological processes. For example, MMP-13 has been shown to enhance the remodeling of 3D collagen matrix, to affect cell morphology, and to promote proliferation of dermal fibroblasts in both in vitro and in vivo models of wound healing (44,55).…”

Section: Discussionmentioning

confidence: 99%

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Distinct biological events generated by ECM proteolysis by two homologous collagenases

Solomonov

Zehorai

Talmi-Frank

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissueremodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition. We revealed striking differences in the motility and signaling patterns, morphology, and gene-expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, in contrast to previous notions, matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. Because ECM proteolysis is an abundant biochemical process that is critical for tissue homoeostasis, these results improve our fundamental understanding its complexity and its impact on cell behavior.T he function and integrity of the extracellular matrix (ECM) is vital for cell behavior as well as for whole-tissue homeostasis (1-4). The ECM undergoes constant remodeling during health and disease states. Its components are regularly being deposited, degraded, or otherwise modified. The highly stable fibrillar collagen type I (Col I) is abundant in many organ-derived ECMs and connective tissues (5, 6); it serves as a tissue scaffold, determining ECM mechanical properties and anchoring other ECM proteins necessary for cell function (7). These processes are orchestrated by multiple remodeling enzymes, among which the matrix metalloproteinase (MMP) family plays an important role. Only a few members of this proteinase family, the collagenases, are able to degrade the resistant fibrillar collagens, i.e., Col I, as well as other ECM molecules (8, 9). The collagenases have conserved amino acids in their zinc-containing catalytic domain (8, 10) and display high structural similarities, as reflected by their functional domain organization. Nevertheless, the complex effects exerted by different MMPs on ECM and cells in vivo remain poorly understood.The enzymatic activity of MMPs, and specifically of collagenases, in vivo is tightly regulated (11), with enzymatic dysregulation causing irreversible damage associated with a variety of diseases. Abnormally elevated levels of MMP-1 or of both MMP-1 and MMP-13 have been associated with different types of cancers and with inflammatory diseases (12-21).Here, we explored the degradation patterns of natural collagenrich ECM by two homologous MMPs and tested the response of cells to intact vs. selectively degraded ECM. We collectively profiled the unique remodeling events caused by two secreted collagenases, MMP-1 and MMP-13, by using biochemical, biophysical, and proteomics tools. We show that these proteases drive morphological, biochemical, and visc...

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Section: Discussionmentioning

confidence: 54%

Section: Mmp-1 and Mmp-13 Produce Distinct Microscale Morphologies Andmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Solomonov

Zehorai

Talmi-Frank

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous studies have addressed the influence of Fibulin-5 in cell proliferation and again, Fibulin-5 showed a dual role as it can display both pro-and anti-proliferative effects. For instance, Fibulin-5 overexpression inhibits endothelial cell proliferation (35,36). Moreover, Spencer et al (37) highlighted the role of Fibulin-5 as an inhibitor of vascular smooth muscle cell proliferation employing the Fbln5-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells

Mohamedi

Fontanil

Solares

et al. 2016

International Journal of Oncology

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Abstract.Fibulins not only function as molecular bridges within the cellular microenvironment but also influence cell behavior. Thus, fibulins may contribute to create a permissive microenvironment for tumor growth but can also stimulate different mechanisms that may impede tumor progression. This is the case with Fibulin-5, which has been shown to display both tumor-promoting and tumor-protective functions by mechanisms that are not totally defined. We show new evidence on the tumor-protective functions displayed by Fibulin-5 in MCF-7, T47D and MDA-MB-231 breast cancer cells including the inhibition of invasion and proliferation capacity and hampering the ability to form mammospheres. Reduction in the level of phosphorylation of Ser residues involved in the nuclear translocation of β-catenin may underlie these antitumor effects. We also found that Fibulin-5 reduces the level of expression of Ki-67, a nuclear protein associated with cell proliferation. Moreover, reduction in Fibulin-5 expression corresponds to an increase of Ki-67 detection in breast tissue samples. Overall, our data provide new insights into the influence of Fibulin-5 to modify breast cancer cell behavior and contribute to better understand the connections between fibulins and cancer.

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Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells

et al. 2018

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Tropomyosins, a family of actin‐associated proteins, bestow actin filaments with distinct biochemical and physical properties which are important for determining cell shape and regulating many cellular processes in eukaryotic cells. Here, we used RNA‐seq to investigate the effect of four tropomyosin isoforms on gene expression in undifferentiated and differentiated rat B35 neuroblastoma cells. In undifferentiated cells, overexpression of tropomyosin isoforms Tpm1.12, Tpm2.1, Tpm3.1, and Tpm4.2 differentially regulates a vast number of genes, clustering into several gene ontology terms. In differentiated cells, tropomyosin overexpression exerts a much weaker influence on overall gene expression. Our findings are particularly compelling because they demonstrate that tropomyosin‐dependent changes are attenuated once the cells are induced to follow a defined path of differentiation. Database Sequence data for public availability are deposited in the European Nucleotide Archive under the accession number PRJEB24136.

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Effects of fibulin-5 on attachment, adhesion, and proliferation of primary human endothelial cells

Cited by 50 publications

References 26 publications

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Distinct biological events generated by ECM proteolysis by two homologous collagenases

Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells

Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells

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