EMILIN1–α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation

Danussi, Carla; Petrucco, A.; Wassermann, Bruna; Pivetta, Eliana; Modica, Teresa Maria Elisa; Belluz, Lisa Del Bel; Colombatti, Alfonso; Spessotto, Paola

doi:10.1083/jcb.201008013

Cited by 87 publications

(132 citation statements)

References 51 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…The higher growth of B16F10 Luc2 cells in Emilin1 À/À mice was expected as melanoma cells express a4 (Fig. 4C) and very weakly a9-integrin (data not shown): the lack of EMILIN1-a4/a9 integrin promotes proliferation (34), and this might be the reason for which B16F10 Luc2 cells gain a growth advantage in an EMILIN1-negative microenvironment.…”

Section: Enhanced Tumor Growth and Lymph Node Metastasis Of Transplanmentioning

confidence: 99%

“…Mouse tissues were excised and processed as previously reported (34). In immunoperoxidase staining, horseradish peroxidase (HRP)-conjugated secondary antibodies (Amersham, GE Healthcare Europe GmbH) were used and visualization was achieved with a diaminobenzidine 3,3 0 -diaminobenzidine (DAB) substrate (Vector Laboratories).…”

Section: Immunostainingmentioning

confidence: 99%

“…The protein content of the samples was determined using Bradford protein assay reagent (BioRad) and Western blot analysis was conducted as previously described (34).…”

Section: Western Blottingmentioning

confidence: 99%

“…EMILIN1 interacts with the a4b1 integrin through its gC1q domain, and it has strong adhesive and migratory properties for different cell types (31)(32)(33). Emilin1 À/À mice display dermal and epidermal hyperproliferation because of the lack of EMILIN1 engagement by a4b1 or a9b1 integrins and the consequent upregulation of pErk1/2 levels through PTEN (34).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion

Danussi

Petrucco

Wassermann

et al. 2012

Cancer Prevention Research

Self Cite

View full text Add to dashboard Cite

The evidence that EMILIN1 (Elastic Microfibril Interface Located proteIN) deficiency in Emilin1 À/À mice caused dermal and epidermal hyperproliferation and an abnormal lymphatic phenotype prompted us to hypothesize the involvement of this extracellular matrix component in tumor development and in lymphatic metastasis. Using the 12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage model of skin carcinogenesis, we found that Emilin1 À/À mice presented an accelerated formation, a higher incidence, and the development of a larger number of tumors compared with their wild-type littermates. EMILIN1-negative tumors showed more Ki67-positive proliferating cells and higher levels of pErk1/2. In these tumors, PTEN expression was lower. Emilin1 À/À mice displayed enhanced lymphangiogenesis both in the tumor and in the sentinel lymph nodes. Accordingly, tumor growth and lymph node metastasis of transplanted syngenic tumors were also increased in Emilin1 À/À mice. In vitro transmigration assays through lymphatic endothelial cells showed that EMILIN1 deficiency greatly facilitated tumor cell trafficking. Overall, these data established that EMILIN1 exerts a protective role in tumor growth, in tumor lymphatic vessel formation, as well as in metastatic spread to lymph nodes and reinforced the importance of its presence in the microenvironment to determine the tumor phenotype. Cancer Prev Res; 5(9); 1131-43. Ó2012 AACR.

show abstract

Section: Enhanced Tumor Growth and Lymph Node Metastasis Of Transplanmentioning

confidence: 99%

Section: Immunostainingmentioning

confidence: 99%

“…The protein content of the samples was determined using Bradford protein assay reagent (BioRad) and Western blot analysis was conducted as previously described (34).…”

Section: Western Blottingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion

Danussi

Petrucco

Wassermann

et al. 2012

Cancer Prevention Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Emilin3 contains the characteristic cysteine-rich EMI domain at the Nterminal end, followed by a region forming three coiled-coil structures at the C-terminal end (Schiavinato et al, 2012). At variance with the other EMILIN/multimerin proteins, Emilin3 is not expressed in the cardiovascular system and it lacks the C-terminal gC1q domain, which is involved in cell attachment and integrin binding (Spessotto et al, 2003;Danussi et al, 2011). Emilin3 expression during mouse development is particularly abundant in the perichondrium of developing bones (Leimeister et al, 2002;Doi et al, 2004;Schiavinato et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals

et al. 2013

View full text Add to dashboard Cite

The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.

show abstract

Review of Integrin‐Targeting Biomaterials in Tissue Engineering

Dhavalikar

Robinson

Lan

et al. 2020

Adv Healthcare Materials

View full text Add to dashboard Cite

The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix-derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin-targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin-mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin-targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

show abstract

EMILIN1–α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation

Abstract: The α4/α9 integrins directly engage the ECM glycoprotein EMILIN1 to inhibit skin cell proliferation upstream of TGF-β signaling.

Cited by 87 publications

References 51 publications

An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion

An EMILIN1-Negative Microenvironment Promotes Tumor Cell Proliferation and Lymph Node Invasion

Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals

Review of Integrin‐Targeting Biomaterials in Tissue Engineering

Contact Info

Product

Resources

About