Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

Abstract

Abstract. Hepatocyte growth factor (HGF) is a key growth factor linked to promoting cancer progression and angiogenesis. The present study identifies repulsive guidance molecule b (RGMb), a bone morphogenetic protein (BMP) co-receptor, as a gene whose expression is regulated by HGF and explores the potential of RGMb to contribute to the process of angiogenesis. Microarray analysis was used to identify HGF responsive genes in HECV endothelial cells, identifying RGMb. RGMb was subsequently targeted using a ribozyme transgene system and its role in angiogenesis assessed using in vitro and in vivo assays. The importance of RGMb in pro-angiogenic responses to HGF and BMP-7 was also assessed. Microarray analysis identified RGMb as a gene upregulated as a result of HGF treatment. Knockdown of RGMb, in HECV cells, had minimal effects on tubule formation, brought about a general, although non-significant increase in cell growth and enhanced cell migration. Similarly, no significant effect of RGMb knockdown was found in vivo using a co-inoculation angiogenesis model. Knockdown of RGMb was, however, found to reduce the responsiveness of HECV cells to HGF treatment and particularly to BMP-7 treatment in regard to the enhanced migratory and tubule formation brought about by these treatments in vitro. Our results indicate that RGMb expression can be influenced by HGF treatment. Whilst this molecule appears to have minimal impact on angiogenic traits individually, it demonstrates an involvement in propagating pro-angiogenic effects of HGF and particularly BMP-7 and thus, may play a role in regulating angiogenic responses to HGF and BMP-7.

Genome-wide association study revealed genomic regions related to white/red earlobe color trait in the Rhode Island Red chickens

“… LOC107052343 NA 50,802,139–50,808,822 6,684 0 NA FAM174A Family with sequence similarity 174 member A 50,808,437–50,822,236 13,800 0 NA CHD1 Chromodomain helicase DNA binding protein 1 51,274,317–51,322,737 48,421 0 Disease related [ 12 , 32 , 33 , 34 ]. RGMB Repulsive guidance molecule family member b 51,334,306–51,349,990 15,685 0 Angiogenesis [ 35 ], breast cancer [ 14 ]. RIOK2 RIO kinase 2 51,538,065–51,550,090 12,026 0 Mitotic progression [ 36 ], cytoplasmic maturation [ 18 ].…”

Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

“…These results indicate that RGMB expression is downregulated as a result of the degree of methylation, which is in line with our observations. Furthermore, there is evidence that RGMB gene expression could be up-regulated by hepatocyte growth factor in HECV endothelial cells [ 19 ]. RGMB is expressed by different cell types and may contribute to tumor growth and progression.…”

“…When the cells reached confluence, the monolayer was electrically wounded at 4 V and 30 kHz for 10 seconds. The in vitro migration rate was determined using a previously described method [ 19 ].…”

In vitro significance of SOCS-3 and SOCS-4 and potential mechanistic links to wound healing

“…A Matrigel tubule formation assay was used to assess the angiogenic potential of human endothelial cells following SOCS-3 and SOCS-4 manipulation. This methodology was adapted from a previously described method 45 . In brief, 50 µl of Matrigel matrix was gently pipetted into the bottom of each well in 96-well plate and incubated until polymerisation had occurred.…”