The Anti-Tumorigenic Activity of Sema3C in the Chick Embryo Chorioallantoic Membrane Model.

Valiulytė Valiulytė,Ribokaitė Ribokaitė,Kazlauskas Kazlauskas,Valančiūtė Valančiūtė,Skauminas Skauminas,Curkūnavičiūtė Curkūnavičiūtė,Vaitkevičiūtė Vaitkevičiūtė

doi:10.3390/ijms20225672

Valiulytė Valiulytė, Ribokaitė Ribokaitė + Show 5 more

Open Access

https://doi.org/10.3390/ijms20225672

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Abstract

Sema3C protein, a member of the class 3 family of secreted semaphorins, play an important role in tumor development by regulating cell proliferation, migration, invasion, and angiogenesis processes. Depending on the type and malignancy grade of the tumor, Sema3C function remains controversial. In this study, we constructed a stably overexpressing Sema3C glioblastoma cell line U87 MG and tested it on the chicken embryo chorioallantoic membrane (CAM) model with the aim to reveal Sema3C protein function on angiogenesis process in ovo. Our experiments showed that Sema3C not only affects angiogenesis of CAM by inhibiting neovascularization but also acts as an anti-tumorigenic molecule by hampering U87 MG cell invasion into mesenchyme. The effects of Sema3C on CAM were similar to the effects of anti-epileptic drug sodium valproate (NaVP). Both, anti-angiogenic and anti-tumorigenic activities of Sema3C were enhanced by the treatment of NaVP and, importantly, were not attributed to the cytotoxic effects. Our studies suggest that Sema3C could be a promising target for glioblastoma treatment.

Highlights

Class 3 semaphorin proteins (Sema3) belong to the family of secreted transmembrane glycoproteins
We revealed that Sema3C protein inhibits microcapillary formation in an in vitro system and the C-terminal arginine of the putative furin cleavage site 742RNRR745 at the basic domain of Sema3C protein is critical for its functions in angiogenesis process [11]
It was demonstrated that higher levels of Sema3C are associated with the progression of astrocytoma [12] and gastric cancer, the latter probably is due to the stimulation of angiogenesis processes [13]

Summary

Introduction

Class 3 semaphorin proteins (Sema3) belong to the family of secreted transmembrane glycoproteins. They consist of seven members (A–G) which are found in most tissues, including cardiovascular, endocrine, gastrointestinal, liver, skeletal, kidney, reproductive, and respiratory systems but mostly in the nervous system, especially during its development [1,2]. It was shown that Sema family members can regulate tumor cell proliferation, migration, survival, metastasis, lymphangiogenesis, and angiogenesis processes in different ways [3,4]. We revealed that Sema3C protein inhibits microcapillary formation in an in vitro system and the C-terminal arginine of the putative furin cleavage site 742RNRR745 at the basic domain of Sema3C protein is critical for its functions in angiogenesis process [11]. Sema3C promotes survival and invasion of glioma stem cells (GSCs) through Rac activation [14]

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