Expression of Autocrine Motility Factor (AMF) and its Receptor, AMFR, in Human Breast Cancer
Wen G. Jiang 1*, Avraham Raz 1, Anthony Douglas-Jones 1 and Robert E. Mansel 1
1 Metastasis and Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom (WGJ,AD-J,REM), and Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (AR)
* To whom correspondence should be addressed. E-mail: jiangw{at}cf.ac.uk.
Submitted on July 18, 2005
Accepted on 21 September 2005
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Abstract |
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Autocrine motility factor (AMF), also known as Glucose-6-phosphate isomerase (GPI) and neuroleukin (NLK), is a factor known to be expressed and secreted by cancer cells and, via an autorine route, stimulates the motility of cancer cells. AMF receptor is a 78 kDa glycoprotein (gp78). The current study investigated the expression of AMF and its receptor in breast cancer and attempted to dissect a clinical link. Breast tumor tissues (n=120) and nonneoplastic normal tissues (n=32) were studied. AMF and AMFR distribution in tissues were assessed using immunohistochemistry. Levels of AMF and AMFR were analyzed using RT-PCR and quantitative PCR. Median follow up of the cohort was 10 years. Mammary epithelial cells, but not stromal and endothelial cells, weakly stained for AMF and AMFR in normal tissues. However, cancer cells showed stronger staining. Furthermore, stromal cells and endothelial cells also showed positive staining in tumor tissues. Both AMF and AMFR transcripts were significantly higher in tumor than in normal tissues (p = 0.003 and p = 0.0001, respectively). AMF, but not AMFR, was significantly higher in high grade (poorly differentiated) tumors. Tumours from patients who died of breast cancer had significantly higher levels of AMF (p = 0.049). Furthermore, tumors of patients who had local recurrence and who died of breast cancer also exhibited high levels of AMFR (p = 0.0435 and p = 0.039) compared with those who remained disease free. Kaplan-Meier survival curves showed that patients with high levels of AMF transcript had a marginal shorter survival (115.6 (81.3-150, 95% CI) months) compared patients with low levels (130.9 (122.4-239.4) months), p = 0.10. However, a significant correlation was seen with the AMFR:CK19 ratio, in which patients with high AMFR:CK19 ratio tumors had a significant shorter survival (101.0 (80.6-121.4) months), compared with those with low ratio (136.0 (123.7-148.2) months, p = 0.0331. In conclusion, autocrine motility factor (ANF) and its receptor are overexpressed in human breast cancer and are negatively associated with clinical outcome of the patients. This strongly indicates that the AMF-AMFR complex plays important role in the progression and that it has a prognostic value of AMF and AMFR in breast cancer.
Key Words:
AMF, AMF receptor, breast cancer, metastasis, prognosis, survival
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