Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer.
BACKGROUND
Angiomotin is a newly discovered molecule that regulates the migration and tubule formation of endothelial cells. It therefore has been implicated in the control of angiogenesis under physiological and pathological conditions. This study examined the expression of angiomotin and its analogues, angiomotin-like 1 (L1) and -like 2 (L2) in breast tumour tissues, and analysed their correlation with angiogenesis and clinical outcomes.


METHODS
Human breast tissues (normal n = 32 and tumours n = 120) were used. The levels of expression of angiomotin, L1 and L2 were determined using reverse transcription PCR. Microvessels were stained using antibodies against PECAM, von Willebrand factor (factor 8, or vWF) and VE-cadherin. The transcript levels of angiomotin and its analogues were assessed against the clinical and pathological background, including long term survival (120 months).


RESULTS
Breast cancer tissues expressed significantly higher levels of angiomotin transcript, compared with normal mammary tissues (33.1 +/- 11 in normal versus 86.5 +/- 13.7 in tumour tissues, p = 0.003). Both L1 and L2 were seen at marginally higher levels in tumour than normal tissues but the difference was not statistically significant. Levels of angiomotin were at significantly higher levels in grade 2 and grade 3 tumours compared with grade 1 (p < 0.01 and p = 0.05 respectively). The levels of angiomotin in tumours from patients who had metastatic disease were also significantly higher than those patients who remained disease free (p = 0.03). Multivariate analysis indicated that angiomotin transcript was an independent prognostic factor (p = 0.031). No significant correlations were seen between angiomotin-L1 and L2 with the clinical outcome. Furthermore, high levels of angiomotin transcript were associated with shorter overall survival (p < 0.05). There was a high degree of correlation between levels of vW factor and that of angiomotin (p < 0.05), but not angiomotin-L1 and angiomotin-L2.


CONCLUSIONS
Angiomotin, a putative endothelial motility factor, is highly expressed in human breast tumour tissues and linked to angiogenesis. It links to the aggressive nature of breast tumours and the long term survival of the patients. These data point angiomotin as being a potential therapeutic target.
Jiang
Wen G
WG
Metastasis and Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Cardiff, UK. jiangw@cf.ac.uk
Watkins
Gareth
G
Douglas-Jones
Anthony
A
Holmgren
Lars
L
Mansel
Robert E
RE
D000091082:Angiomotins; D015703:Antigens, CD; D001365:Axilla; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D015820:Cadherins / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000032:analysis*; D008833:Microcirculation / Q000473:pathology; D008840:Microfilament Proteins; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011379:Prognosis; D000099152:Cadherin 5
D000091082:Angiomotins; D015703:Antigens, CD; D015820:Cadherins; D002352:Carrier Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5; C423985:AMOT protein, human; C510063:AMOTL1 protein, human; C508566:AMOTL2 protein, human