N-glycosylation status of beta-haptoglobin in sera of patients with prostate cancer vs. benign prostate diseases.
N-glycosylation status of purified beta-haptoglobin separated from sera of patients with prostate cancer was studied in comparison to that of sera from patients with benign prostate diseases, or normal subjects. Two different approaches, as summarized below, one based on binding of lectins and antibodies to beta-haptoglobin, the other on mass spectrometry of released N-linked glycans from beta-haptoglobin, were performed. Some of the results were useful for distinction of prostate cancer vs. benign prostate diseases. i) Binding of Phaseolus vulgaris-L lectin (PHA-L), defining the GlcNAcbeta6Manalpha6Man side chain present in tri- or tetra-antennary N-linked glycans, to beta-haptoglobin was higher for cases of prostate cancer and high-grade prostate intraepithelial neoplasia than for benign diseases. Binding of Aleuria aurantia lectin (AAL) defining Fucalpha3-, alpha4-, or alpha6-GlcNAc, or monoclonal antibody directed to sialyl-Le(x), to beta-haptoglobin was also higher for some of the cancer cases than for benign diseases. Many other lectins and antibodies showed no binding to beta-haptoglobin, or showed no significant difference between cancer vs. benign diseases. ii) Mass spectrometric analysis of N-linked glycans of beta-haptoglobin released by Peptide N-glycosidase-F showed enhanced expression of monosialyl tri-antennary structures in prostate cancer cases. Thus, binding of PHA-L to affinity-purified beta-haptoglobin from sera of patients could lead to development of useful tools for differential diagnosis of prostate cancer vs. benign prostate diseases.
Yoon
Seon-Joo
SJ
Division of Biomembrane Research, Pacific Northwest Research Institute and Departments of Pathobiology and Global Health, University of Washington, Seattle, WA 98122, USA.
Park
Seung-Yeol
SY
Pang
Poh-Choo
PC
Gallagher
Jenni
J
Gottesman
James E
JE
Dell
Anne
A
Kim
Jung-Hoe
JH
Hakomori
Sen-Itiroh
SI
D000368:Aged; D002845:Chromatography / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000737:chemistry; D006031:Glycosylation; D006242:Haptoglobins / Q000096:biosynthesis*; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D027805:Phaseolus / Q000378:metabolism; D011469:Prostatic Diseases / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D000939:Epitopes; D006242:Haptoglobins; D037102:Lectins