Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis

Capuano, Alessandra; Pivetta, Eliana; Sartori, Giulio; Bosisio, Giulia; Favero, Andrea; Cover, Eleonora; Andreuzzi, Eva; Colombatti, Alfonso; Cannizzaro, Renato; Scanziani, Eugenio; Minoli, Lucia; Bucciotti, Francesco; Lopez, Ana Isabel Amor; Gaspardo, K.; Doliana, Roberto; Mongiat, Maurizio; Spessotto, Paola

doi:10.1016/j.matbio.2019.08.006

Cited by 28 publications

(21 citation statements)

References 55 publications

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“…Indeed, expression of EMILIN-1 has already been described with suppressive activities in epithelial cells, colitis and colon carcinogenesis [17, 42]. Importantly, analysis in EMILIN-1 KO showed that its ablation in the microenvironment promoted tumor progression in skin, melanoma and colon cancer models [18].…”

Section: Discussionmentioning

confidence: 99%

“…Given that sEVs-derived from melanoma cells promote lymphangiogenesis, extracellular matrix (ECM) remodeling, immunosuppression and metastasis in LNs [15, 16], in this work we wanted to analyze if lymph the node metastatic melanoma model B16-F1R2 has a specific signature that may favor tumor cell survival in lymph nodes. We have found a specific signature of genes over-expressed in cells and proteins hyper-secreted in sEVs including EMILIN-1, a protein involved in lymph node physiology and pathology [17, 18]. We found that EMILIN-1 is proteolyzed and secreted in sEVs as a mechanism to reduce its intracellular levels in this cell line.…”

Section: Introductionmentioning

confidence: 98%

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Inactivation of EMILIN-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis

Lopez

Mazariegos

Capuano

et al. 2021

Preprint

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Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not defined completely. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth and metastasis in mouse melanoma models. Finally, analysis in human melanoma samples showed that tumor cells with high levels of EMILIN-1 are reduced in metastatic lesions compared to primary tumors or nevi. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Inactivation of EMILIN-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis

Lopez

Mazariegos

Capuano

et al. 2021

Preprint

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“…(265)(266)(267). In addition, EMILIN2 promotes the formation of tumor-associated vessels in melanoma (268), and EMILIN1 exerts an oncosuppressive role in colon and skin (269,270).…”

Section: Mcps As Therapeutic Targetsmentioning

confidence: 99%

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

et al. 2020

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The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCPs) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets. Research.

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“…Through the engagement of cell surface receptors, interaction with other ECM molecules and release of growth factors/cytokines upon remodeling, the ECM significantly influences the behavior of tumor cells, as well as other tumor-associated cell types such as infiltrating leukocytes, vascular endothelial cells, pericytes, and lymphatic endothelial cells [ 28 , 65 , 66 , 67 ].…”

Section: Ecm As a Multi-armed Warrior In Scc Disseminationmentioning

confidence: 99%

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

Fejza

Camicia

Poletto

et al. 2021

Cancers

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Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this review. These tumors are often refractory to current therapeutic approaches with poor patient outcome. The most important prognostic determinant of SCC tumors is the presence of distant metastasis, significantly correlating with low patient survival rates. Rapidly emerging evidence indicate that the extracellular matrix (ECM) composition and remodeling profoundly affect SSC metastatic dissemination. In this review, we will summarize the current knowledge on the role of ECM and its remodeling enzymes in affecting the growth and dissemination of UADT SCC. Taken together, these published evidence suggest that a thorough analysis of the ECM composition in the UADT SCC microenvironment may help disclosing the mechanism of resistance to the treatments and help defining possible targets for clinical intervention.

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Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis

Cited by 28 publications

References 55 publications

Inactivation of EMILIN-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis

Inactivation of EMILIN-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

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