New function ofTSGA10gene in angiogenesis and tumor metastasis: a response to a challengeable paradox

Abstract

Several studies have shown that testis-specific gene antigen (TSGA10) could be considered as a cancer testis antigen (CTA), except for one study which has identified it as a tumor suppressor gene. In order to exert its function, TSGA10 interacts closely with hypoxia inducible factor (HIF-1α) and since this interaction is still not completely defined, the exact role of TSGA10 in angiogenesis and invasion is also under question. The current study was conducted to investigate the function of TSGA10 gene and evaluate its potential effects on tumor angiogenesis and invasion. To do so, TSGA10 vector was designed for a stable transfection in HeLa cells, and then clonal selection was applied. The efficiency of transfection and the role of TSGA10 in abovementioned targets were evaluated by real-time PCR, western blot, zymography and ELISA tests in both normoxia and hypoxia. Invasion, migration and angiogenesis were assessed. Three-dimensional model of TSGA10 protein was accurately built in which TSGA10 docked to 2 domains of HIF-1α. Increased expression of TSGA10 correlated with decreased HIF-1α transcriptional activity and inhibited angiogenesis and HeLa cells invasion in normoxia as well as hypoxia. Docking analysis indicated that binding affinity of TSGA10 with TAD-C (CBP) domain of HIF-1α would be stronger than that with PAS-B domain. Our findings showed that overexpression of TSGA10 would induce disruption of HIF-1α axis and exert potent inhibitory effects on tumor angiogenesis and metastasis. Therefore, TSGA10 could be considered as a potent therapeutic candidate, prognostic factor and a cancer management tool.

Identification and expression analysis of zebrafish testis-specific gene 10 (tsga10)

“…TSGA10 gene in human localizes to region q11.2 of chromosome 2 and is mainly expressed in testis and some tumors (Behnam et al, 2009, Mobasheri et al, 2007, Modarressi et al, 2004, Modarressi et al, 2001. In recent years, intense efforts to identify the function of TSGA10 led to the discovery of the inhibitory effect of TSGA10 on tumor angiogenesis (Mansouri et al, 2016). Previous studies have shown that TSGA10 is expressed during spermatogenesis (in testis), embryogenesis (undifferentiated embryonic stem cells), brain development, and in different types of cancer (Behnam et al, 2009, Miryounesi et al, 2014, Mobasheri et al, 2007, Mobasheri et al, 2006, Reimand et al, 2008, Smith et al, 2011.…”

“…HIF-1a activates the transcription of genes involved in critical aspects of cancer development, such as angiogenesis and cell survival (Semenza, 2003). A recent study has shown that TSGA10 overexpression decreases HIF-1a transcriptional activity and inhibits angiogenesis, cell growth, and invasion of HeLa cells (Mansouri et al, 2016). Although these studies support the concept that TSGA10 has a repressive role in angiogenesis, these are still insufficient to explain the precise role of TSGA10 particularly in a living organism.…”

All‐trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo

“…Cells were monitored after 48 hours. Sprouts formation was measured using NIH Image J software and presented as a percentage …”

Anti‐angiogenesis effect of β‐D‐mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model

“…Angiogenesis is also of great importance during pathological conditions like diabetic retinopathy, cancer development and chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis where excessive angiogenesis contributes to pathology . Angiogenesis is essential for tumor growth and metastasis and it has been shown that without angiogenesis malignant epithelial tumors could not grow more than several cubic millimeters . Malignant tumors need to recruit new blood vessels for their growth, invasion, and metastasis .…”

“…RASTEGARI-POUYANI ET Al. been shown that without angiogenesis malignant epithelial tumors could not grow more than several cubic millimeters. 5 Malignant tumors need to recruit new blood vessels for their growth, invasion, and metastasis. 6 There is strong evidence demonstrating the association between angiogenesis and inflammation in pathological conditions such as diabetes, rheumatoid arthritis (RA), psoriasis, Crohn's disease and finally cancer.…”