Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

Table 5

Altered expression of Eph receptors and ephrin ligands in prostate cancer.

Eph receptor/ephrin ligand	Preferred molecular interaction	↑/↓ relative to normal tissue	Mechanism	Reference
EphA1		↓	(i) Lower level of EphA1 transcript levels in primary prostate tumor cells compared to normal prostate epithelium	[86]
EphA2	Ephrin-A1	↑	(i) Highest levels of EphA2 staining in prostatic adenocarcinoma followed by high grade intraepithelial neoplasia with low positive EphA2 staining in benign tissue; (ii) EphA2 stimulation with ephrin-A1 resulted in inhibition of PC3 migration	[87, 88]
EphA3		↑	(i) Increase level of EphA3 in androgen independent prostate cancer cells compared to androgen dependent prostate cancer cells; (ii) Inactivation of AMP-activated protein kinase (AMPK) resulted in transformation of prostate cancer cell line and upregulation of EphA3 mRNA	[89, 90]
EphA4	Ephrin-A5	↑	(i) cDNA microarray shows EphA4 elevation in prostatic intraepithelial neoplasia and prostate cancer; (1) SiRNA knockout of EphA4 resulted in decrease cell viability and colony formation; (ii) EphA4 stimulation with ephrin-A5 resulted in inhibition of PC3 migration; (iii) EphA4 may be regulated by ERBB3/HER3; (1) Knockdown of ERBB3 in DU-145 resulted in downregulation of EphA4	[88, 91, 92]
EphB2		Mutant expression of inactive EphB2 in prostate cancer	(i) Two mutations in extracellular part of EphB2 and six mutations in the intracellular part of EphB2; (1) Extracellular mutation: R199H, A279S; (2) Intracellular mutation: D679N, 2139+2T→C, Q723X, T909M, K1019X, and 3051delA; (ii) Loss of EphB2 in primary prostate tumor cells compared to normal prostate epithelium cells	[86, 93]
Ephrin-A1		↓	(i) Higher Gleason score correlate with lower levels of ephrin-A1	[94]
Ephrin-A5	EphA4; EphA7; EphB1; EphB2	↓	(i) Proteomic analysis of LnCaP cell culture media demonstrated increased levels of ephrin-A5 post androgen exposure; (ii) Lower levels of ephin-A5 correlated with shorter predicated survival time	[95, 96]