Identification of a novel type of CA19-9 carrier in human bile and sera of cancer patients: an implication of the involvement in nonsecretory exocytosis.
Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatic cancer. Although the CA19-9 level is measured using anti-sialyl Lewis A antibodies, it remains unknown which molecules carry CA19-9 other than mucins. Here we report the identification and characterization of a novel type of CA19-9 carrier, BGM (bile globular membrane), which is thought to exist in normal bile and to be secreted into sera of patients with pancreatic cancer. We purified the BGM from bile juice using a β-casein column because surface plasmon resonance analysis could detect such carrier vesicles binding to β-casein in sera of patients with pancreatic cancer. We identified characteristic molecules for BGM such as AHNAK (desmoykoin) and a novel golgin family member, CABIN (CAsein Binding domain integral protein with golgIN motif) by mass spectrometry analysis. BGM was detected in the sera of patients with pancreatic cancer as well as athymic mice with transplanted pancreatic cancer cells. Down regulation of CABIN inhibited the secretion of CA19-9 on BGM in pancreatic cancer cell lines. We measured and visualized BGM in sera of patients with cancer. Thus, BGM might be another CA19-9 carrier (glyco-lipids on membrane vesicles) other than mucins and could be applied to the diagnosis of pancreatic cancer.
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Japan.
Naofumi
N
Uozumi
Congxiao
C
Gao
Tomoko
T
Yoshioka
Miyako
M
Nakano
Kenta
K
Moriwaki
Tsutomu
T
Nakagawa
Tomomi
T
Masuda
Makoto
M
Tanabe
Eiji
E
Miyoshi
D000595:Amino Acid Sequence; D000818:Animals; D001646:Bile / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D018395:CA-19-9 Antigen / Q000032:analysis*; D002364:Caseins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005089:Exocytosis; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014183:Transplantation, Heterologous; D022161:Transport Vesicles / Q000737:chemistry* / Q000378:metabolism
C075176:AHNAK protein, human; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002364:Caseins; D008565:Membrane Proteins; D009363:Neoplasm Proteins