Mechanism of host cell membrane modification by tumour: a model for paraneoplastic syndromes.
A not well-appreciated but clinically important aspect of malignant tumours is their effects on distantly located host cells. The effects, termed paraneoplastic syndromes, also pose an intriguing mechanistic problem: how do malignant cells influence properties of host cells not in contact with them? Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma exhibit higher agglutinability with concanavalin A (Con A) than the cells from normal animals. Since the tumour and the red cells are not in contact, the enhanced agglutinability of the latter is a paraneoplastic effect. The mechanism by which the tumour brings about this effect is investigated as a model for paraneoplastic syndromes. The cell-free ascites fluid is able to impart high agglutinability on cells from normal animals in vitro. Also, when injected intraperitoneally in normal animals, the ascites fluid is able to enhance the agglutinability of erythrocytes in circulation. Apparently the tumour produces a substance(s) that appears in the ascites fluid and is able to diffuse into circulation, explaining the mechanism by which it can reach distant sites. From the cell-free ascites fluid three fractions have been isolated that are active in vitro. Of these, only one showed activity in vivo. From this fraction, a glycoprotein has been purified to homogeneity that confers maximal Con A-agglutinability on normal erythrocytes at 8 x 10(-7)M, at which concentration 6,400 molecules bind per cell. The protein has a molecular weight of 600 kDa in the native state and a pI of 5.35. It is made up of 4 identical subunits of Mr 170,000. It is detected in the plasma of tumour-bearing but not normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Kalraiya
R D
RD
Biological Chemistry Division, Tata Memorial Centre, Parel, Bombay.
Iyer
S S
SS
Chati
A
A
Mehta
N G
NG
D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D003208:Concanavalin A / Q000378:metabolism; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004903:Erythrocyte Aggregation; D004910:Erythrocyte Membrane / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000378:metabolism*; D051381:Rats; D012517:Sarcoma, Yoshida; D000511:alpha-Macroglobulins
D006023:Glycoproteins; D009363:Neoplasm Proteins; D000511:alpha-Macroglobulins; D003208:Concanavalin A