Annexin 2 and hemorrhagic disorder in vascular intimal carcinomatosis.
Vascular intimal carcinomatosis refers to a characteristic tumor proliferation on vascular intima that replaces normal endothelium. This pathological event of unknown cause is quite different from tumor thrombotic microangiopathy due to the absence of thrombi on the tumor cell surfaces. We analyzed renal transitional cell carcinoma cases with metastasis to the main pulmonary arteries and marked hyperfibrino(geno)lysis. The fibrinogen-derived products from patients' plasma were identified as D1A/gamma, D1/gamma, and D1/beta by immunoblotting with the NH2-terminus of the fragment D specific antibody JIF-23. In all cases, the neoplastic cells with vascular intimal carcinomatosis were stained positive for anti-human annexin 2, which is a unique cell surface co-receptor for plasminogen and tissue-type plasminogen activator. In contrast, normal renal pelvic mucosa or renal transitional cell carcinoma without vascular intimal carcinomatosis did not express any annexin 2. The isolated transitional cell carcinoma cells contained annexin 2 mRNA and expressed its protein. Anti-annexin 2 antibody and transfection of annexin 2 small interfering RNA into these carcinoma cells significantly inhibited tissue-type plasminogen activator dependent plasmin generation. These findings suggest that annexin 2 mediated fibrinolysis on the transitional cell carcinoma cells may play a role in inducing hemorrhagic disorder in vascular intimal carcinomatosis.
Madoiwa
Seiji
S
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan.
Someya
Tsutomu
T
Hironaka
Mitsugu
M
Kobayashi
Hiroshi
H
Ohmori
Tsukasa
T
Mimuro
Jun
J
Sugiyama
Yukihiko
Y
Morita
Tatsuo
T
Nishimura
Yoshioki
Y
Tarumoto
Takahisa
T
Ozawa
Keiya
K
Saito
Ken
K
Sakata
Yoichi
Y
D000328:Adult; D017306:Annexin A2 / Q000032:analysis* / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis; D005342:Fibrinolysis; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011651:Pulmonary Artery / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D010959:Tissue Plasminogen Activator; D017539:Tunica Intima / Q000473:pathology*; D019043:Vascular Neoplasms / Q000737:chemistry / Q000150:complications* / Q000556:secondary
C472822:ANXA2 protein, human; D017306:Annexin A2; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin