A novel secreted tumor antigen with a glycosylphosphatidylinositol-anchored structure ubiquitously expressed in human cancers.
In a search for novel genes expressed in human cancers, we identified one gene from an assembled expressed sequence tag database. Northern blot analysis revealed that the gene, termed alcan, was expressed in various types of human cancer cell lines and in the fetus, but not in normal tissues. The alcan gene is located on chromosome 6 and is encoded on a 246-amino-acid protein with weak homology to classical major histocompatibility complex class I. Its gene product, ALCAN, had hydrophobic amino acid clusters at both the N- and C-terminal regions and was predicted to be a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Flow cytometric analysis revealed that ALCAN was detected on the surface of human cancer cells and on alcan-transfected CHO-K1 cells. ALCAN was also secreted from these cells, suggesting that some portion of the molecules was secreted by enzymatic cleavage by, for example, phospholipases. Mutational analysis of ALCAN suggested that the GPI-anchored position was the Ser(216) residue. These findings indicate that ALCAN may be a potential target for cancer diagnosis or therapy.
Onda
H
H
Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., 10 Wadai Tsukuba, Ibaraki 300-4293, Japan. Onda_Haruo@takeda.co.jp
Ohkubo
S
S
Shintani
Y
Y
Ogi
K
K
Kikuchi
K
K
Tanaka
H
H
Yamamoto
K
K
Tsuji
I
I
Ishibashi
Y
Y
Yamada
T
T
Kitada
C
C
Suzuki
N
N
Sawada
H
H
Nishimura
O
O
Fujino
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D006224:Cricetinae; D004252:DNA Mutational Analysis; D005260:Female; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012694:Serine; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C423230:ULBP2 protein, human; D012694:Serine