Loss of Multimerin-2 and EMILIN-2 Expression in Gastric Cancer Associate with Altered Angiogenesis

Abstract

Gastric cancer is a deadly tumor and a relatively common disease worldwide. Surgical resection and chemotherapy are the main clinical options to treat this type of disease, however the median overall survival rate is limited to one year. Thus, the development of new therapies is a highly necessary clinical need. Angiogenesis is a promising target for this tumor type, however clinical trials with the use of anti-angiogenic drugs have so far not met expectations. Therefore, it is important to better characterize the expression of molecules whose expression levels may impact on the efficacy of the treatments. In this study the characteristics of the gastric tumor associated blood vessels were first assessed by endomicroscopy. Next, we analyzed the expression of Multimerin-2, EMILIN-2 and EMILIN-1, three molecules of the EMI Domain ENdowed (EDEN) protein family. These molecules play important functions in the tumor microenvironment, affecting cancer progression both directly and indirectly impinging on angiogenesis and lymphangiogenesis. All the molecules were highly expressed in the normal mucosa whereas in a number of patients their expression was altered. We consider that better characterizing the gastric tumor microenvironment and the quality of the vasculature may achieve effective patient tailored therapies.

Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma

“…EMILIN/Multimerins are a unique family of glycoproteins present in the extracellular matrix (Colombatti et al, 2012). Previous research demonstrated the role of EMILIN/ Multimerins in regulating tumor growth progression (Andreuzzi et al, 2018;Rabajdova et al, 2016) including the association of EMILIN3 in LGG survival rates (Zeng et al, 2018). LGG is a chronic disease characterized by tumor migration, infiltration of the brain's connectome and recurrence after conventional treatment (Delgado-Lopez et al, 2017).…”

“…Notably, previous research has reported that high expression of EMILIN3 was confirmed to predict poor survival in LGG (Zeng et al, 2018). Also, recent studies have confirmed that the appearance of Multimerin-2 and EMILIN-2 is significantly altered in gastric cancer patients (Andreuzzi et al, 2018) and EMILIN2 has a bidirectional role in tumor micro environments (Mongiat et al, 2010). Although EMILIN/Multimerins act as promising biomarkers in tumor development, heir expression pattern, molecular function and prognostic value in LGG have not been investigated.…”

Peer Review #1 of "Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma (v0.1)"

“…LGG (Zeng et al 2018). And, recent studies have confirmed that the appearance of Multimerin-2 and EMILIN-2 is significantly altered in gastric cancer patients (Andreuzzi et al 2018) and EMILIN2 has a bidirectional role in tumor microenvironments (Mongiat et al 2010). Although EMILIN/Multimerins act as promising biomarkers in tumor development, heir expression pattern, molecular function and prognostic value in LGG have not been investigated.…”

Peer Review #2 of "Expression patterns and the prognostic value of the EMILIN/Multimerin family members in low-grade glioma (v0.2)"

“…The ratios of 188 genetic alterations in EMILIN/Multimerins range from 0.4% to 1.4% for each member (EMILIN1 189 0.4%, EMILIN2 1.4%, EMILIN3 0.4%, MMRN1 0.4% and MMRN2 1.4%; Figure 8B). (Andreuzzi et al 2018;Rabajdova et al 2016) including the 224 association of EMILIN3 in LGG survival rates (Zeng et al 2018).…”

“…EMILIN1, the most notable member of the EMILIN/Multimerin family, was overexpressed 230 in many organs, including blood vessels, lymphatic vessels, connective tissues, cardiovascular 231 system and the central nervous system (Modica et al 2017). The main functions of EMILIN1 232 include cell adhesion and migration in tumor growth (Capuano et al 2018). Modica, TME et 233 al (Modica et al 2017) founded that EMILIN1 can silences the RAS-ERK pathway via alpha4beta1 234 integrin, decreasing tumor cell growth.…”