Senger D R, Perruzzi C A, Papadopoulos A, Tenen D G
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
Biochim Biophys Acta. 1989 Jun 13;996(1-2):43-8. doi: 10.1016/0167-4838(89)90092-7.
A wide variety of rodent and human tumor cells secrete antigenically related phosphoproteins with molecular weights (Mr) of approximately 58,000 (hamster), 62,000 (rat, mouse), 67,000 (human) (Senger, D.R. and Perruzzi, C.A. (1985) Cancer Res. 45, 5818-5823). Expression of these phosphoproteins is transformation-related; tumor cells produce at least 10-fold or more of this protein as compared to their normal or untransformed counterparts. N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein indicate that it is identical to rat osteopontin, a bone protein with an Arg-Gly-Asp cell-binding sequence (Oldberg, A., Franzen, A. and Heinegard, D. (1986) Proc. Natl. Acad. Sci. USA 83, 8819-8823). Antibody raised to the Mr 62,000 rat tumor-secreted phosphoprotein was found to bind Mr 75,000 and Mr 35,000 components of human milk, indicating that milk contains antigenically related proteins. The Mr 75,000 protein, which is present in human milk at concentrations ranging from 3 to 10 micrograms/ml, has been purified to homogeneity. The Mr 35,000 component is apparently derived from the Mr 75,000 protein by proteolytic cleavage, and this cleavage also occurs in vitro in the presence of thrombin. N-terminal and internal amino acid sequences were derived from the Mr 75,000 milk protein and found to be similar (12/21 residues) to N-terminal and internal sequences derived from the rat tumor-secreted phosphoprotein and osteopontin. Moreover, sequence derived from the N-terminus of the human milk protein is identical to that of human bone sialoprotein I (the likely human homolog of rat osteopontin) (Fisher, L.W., Hawkins, G.R., Tuross, N. and Termine, J.D. (1987) J. Biol. Chem. 262, 9702-9708).
多种啮齿动物和人类肿瘤细胞分泌抗原相关的磷蛋白，其分子量（Mr）约为58,000（仓鼠）、62,000（大鼠、小鼠）、67,000（人类）（森格尔，D.R.和佩鲁齐，C.A.（1985年）《癌症研究》45卷，5818 - 5823页）。这些磷蛋白的表达与细胞转化相关；与正常或未转化的对应细胞相比，肿瘤细胞产生的这种蛋白至少多10倍或更多。从大鼠肿瘤分泌的磷蛋白获得的N端和内部序列表明，它与大鼠骨桥蛋白相同，骨桥蛋白是一种具有精氨酸 - 甘氨酸 - 天冬氨酸细胞结合序列的骨蛋白（奥尔德伯格，A.、弗兰岑，A.和海内加德，D.（1986年）《美国国家科学院院刊》83卷，8819 - 8823页）。发现针对大鼠肿瘤分泌的62,000 Mr磷蛋白产生的抗体能与人乳中的75,000 Mr和35,000 Mr成分结合，表明乳汁中含有抗原相关蛋白。人乳中浓度为3至10微克/毫升的75,000 Mr蛋白已被纯化至同质。35,000 Mr成分显然是由75,000 Mr蛋白经蛋白水解裂解产生的，并且这种裂解在凝血酶存在的情况下也会在体外发生。从75,000 Mr乳蛋白获得了N端和内部氨基酸序列，发现与从大鼠肿瘤分泌的磷蛋白和骨桥蛋白获得的N端和内部序列相似（21个残基中有12个相同）。此外，从人乳蛋白N端获得的序列与人类骨唾液酸蛋白I（大鼠骨桥蛋白可能的人类同源物）的序列相同（费舍尔，L.W.、霍金斯，G.R.、图罗斯，N.和特尔米内，J.D.（1987年）《生物化学杂志》262卷，9702 - 9708页）。
