Prognostic Significance of EDIL3 Expression and Correlation with Mesenchymal Phenotype and Microvessel Density in Lung Adenocarcinoma

Jeong, Dongjun; Ban, Seona; Oh, Seung-Hyun; Lee, Su Jin; Park, Sung Yong; Koh, Young Wha

doi:10.1038/s41598-017-08851-9

Cited by 34 publications

(28 citation statements)

References 40 publications

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“…DEL-1, a glycoprotein secreted by many cell types, is upregulated upon hypoxia or injury, has been implicated in vascular remodeling, and induces integrin signaling (Hidai et al, 1998;Penta et al, 1999). In patients with adenocarcinoma, DEL-1 is an independent prognostic factor for overall survival (Jeong et al, 2017). Its role in melanoma remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

Wenzina

Holzner

Puujalka

et al. 2020

Journal of Investigative Dermatology

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Melanoma cells can switch between distinct gene expression profiles, resulting in proliferative or invasive phenotypes. Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. CDH1 negativity was identified as a surrogate marker for the invasive phenotype. CDH1 expression could be turned on and off by modulating activity of p38 or its downstream target MK2, suggesting that this pathway controls melanoma progression. Mechanistically, MK2 inhibition prevented melanoma-induced vascular barrier disruption, reduced the expression of PODXL and DEL-1, and prevented vascular dissemination in vivo. PODXL and DEL-1 expression in patients with melanoma were associated with poor survival and thus can be used as prognostic markers. Downstream targets of MK2 may thus serve as candidate therapeutics.

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Section: Discussionmentioning

confidence: 99%

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

Wenzina

Holzner

Puujalka

et al. 2020

Journal of Investigative Dermatology

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“…Based on the multivariate analysis, they concluded that EDIL3 acts as an independent predictor of overall survival in lung adenocarcinoma. Thus, the analyzed protein is closely related to angiogenesis, the development of tumor mass in lung adenocarcinoma and mesenchymal phenotype [18].…”

Section: Discussionmentioning

confidence: 99%

“…It also plays an important role in modulating the adhesion of immunocytes through interactions with leukocyte-specific integrins [11]. Changes in the expression profile of EDIL3 were observed in hepatocellular carcinoma [12, 13], pancreatic cancer [14], colorectal cancer [15], bladder cancer [16], breast cancer [17] and lung cancer [18]. The key aspect of cancer transformation is angiogenesis [19], during which the loss of balance between the level of pro- and anti-angiogenic factors is observed [20].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Changes in the Expression Pattern of EDIL3 in Different Grades of Endometrial Cancer

Opławski¹,

Dziobek

Zmarzły

et al. 2019

CPB

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Background: EDIL3 is an extracellular matrix protein that plays a key role in angiogenesis. Changes in the pattern of its expression also affect cellular processes and the tumor microenvironment. Elevated level of EDIL3 is considered an unfavorable prognostic marker of survival. Objective: The aim of this study was to evaluate the changes in EDIL3 expression in endometrial cancer at various degrees of its differentiation (G1-G3) and to discuss its potential role as a molecular diagnostic marker and therapeutic target. Methods: The study group consisted of 45 patients with endometrial cancer: G1, 17; G2, 15; G3, 13. The control group (C) included 15 patients without neoplastic changes. The expression of EDIL3 was assessed using immunohistochemistry. Statistical analysis was performed using the Statistica 12 PL software (p<0.05). Results: Analysis of EDIL3 expression showed that the average optical density of the reaction product in G1 reached 130% of the control, while the values in G2 and G3 were 153% and 158%, respectively. Regardless of the endometrial cancer grade, an increase in EDIL3 level was observed compared to the control. Conclusion: In our study, we demonstrated overexpression of EDIL3 protein in endometrial cancer. Differences in expression between degrees of tumor differentiation suggest the potential of using changes in EDIL3 level as a new complementary diagnostic marker and target for anti-angiogenic therapy.

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“…EDIL3 acts as a pro-angiogenic factor, mediator of the immune and anti-inflammatory response, and a regulator of endothelial cell adhesion and migration [13][14][15] . It has been reported that EDIL3 is overexpressed in several tumor types, including bladder, pancreas, breast, and liver carcinomas, and associates with tumor progression and poor prognosis [16][17][18][19][20][21][22][23] . EDIL3 has been identified as a novel regulator of EMT in hepatocellular carcinoma cells, as the increased expression of EDIL3 by miRNA-137 downregulation triggers ERK and TGF-β activation via interaction with the integrin α V β 3 ( 20 ).…”

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confidence: 99%

“…This integrin plays a crucial role in the growth of brain metastasis in breast cancer 24 . Also, EDIL3 has been identified in the extracellular vesicles of breast cancer cells that may be used for early breast cancer detection in the plasma of patients [21][22][23][24][25] .…”

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confidence: 99%

EDIL3 promotes epithelial–mesenchymal transition and paclitaxel resistance through its interaction with integrin αVβ3 in cancer cells

et al. 2020

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Epithelial–mesenchymal transition (EMT) has recently been associated with tumor progression, metastasis, and chemotherapy resistance in several tumor types. We performed a differential gene expression analysis comparing paclitaxel-resistant vs. paclitaxel-sensitive breast cancer cells that showed the upregulation of EDIL3 (EGF Like Repeats and Discoidin I Like Domains Protein 3). This gene codifies an extracellular matrix protein that has been identified as a novel regulator of EMT, so we studied its role in tumor progression and paclitaxel response. Our results demonstrated that EDIL3 expression levels were increased in paclitaxel-resistant breast and prostate cancer cells, and in subsets of high-grade breast and prostate tumors. Moreover, we observed that EDIL3 modulated the expression of EMT markers and this was impaired by cilengitide, which blocks the EDIL3–integrin αVβ3 interaction. EDIL3 knockdown reverted EMT and sensitized cells to paclitaxel. In contrast, EDIL3 overexpression or the culture of cells in the presence of EDIL3-enriched medium induced EMT and paclitaxel resistance. Adding cilengitide resensitized these cells to paclitaxel treatment. In summary, EDIL3 may contribute to EMT and paclitaxel resistance through autocrine or paracrine signaling in cancer cells. Blockade of EDIL3–integrin αVβ3 interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

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Prognostic Significance of EDIL3 Expression and Correlation with Mesenchymal Phenotype and Microvessel Density in Lung Adenocarcinoma

Cited by 34 publications

References 40 publications

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

Evaluation of Changes in the Expression Pattern of EDIL3 in Different Grades of Endometrial Cancer

EDIL3 promotes epithelial–mesenchymal transition and paclitaxel resistance through its interaction with integrin αVβ3 in cancer cells

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