© 1991 S. Kargcr AG, Basel 10 10-4283/91 /0 123-0184S2.75/0
Tumor Biol 1991 ; 12:184-188
Production of 13 Plasma Proteins by Human Testicular Yolk Sac Tumor Transplanted into Nude Mice Shinzo Nishi*, Toshiba Nishitah, Kiyoshi Ohkawac 3 Department of Biochemistry, Hokkaido University School of Medicine, Sapporo; b Department of Veterinary Physiology 1, Azabu University School of Veterinary, Sagamihara; cDepartment of Biochemistry, Jikei University School of Medicine, Tokyo, Japan
Key Words. Plasma protein • Yolk sac tumor • Nude mouse Abstract. Thirteen human proteins were found in plasma and cystic fluid o f mice bearing human testicular yolk sac tumor. Six o f them, a-fetoprotein, prealbumin, albumin, a [-anti trypsin, hemopexin and transferrin, had been previously demonstrated to be produced by yolk sac tumors. The syntheses o f the remaining seven, namely apolipoprotein A l, retinol binding protein, c^HS-glycoprotein, haptoglobin, apolipoprotein B, C5 component and anti hemophilic factor, have been demonstrated for the first time.
It is well established that human yolk sac tumors produce a-fetoprotein (AFP) [1-6] and several other plasma proteins [2-4], Us ing immunohistochemical techniques, Shirai et al. [2] showed that such tumors produced AFP, albumin (Alb), apantitrypsin (aiAT) and transferrin (Tf). We previously reported that testicular yolk sac tumor cultured with radiolabelled amino acid produced AFP, Alb and T f [3]. Immunoelectrophoretic analyses o f the plasma o f nude mice bearing yolk sac tumors demonstrated the synthesis o f preal bumin (PA) and hemopexin (Hpx) in addi tion to AFP, Alb, a|A T and T f [4], In the present study, we explored the production o f
plasma proteins by human testicular yolk sac tumor serially transplanted into nude mice using antisera against 31 human plasma pro teins. Seven o f 13 proteins detected, namely apolipoprotein A l (ALpA), retinol-binding protein (RBP), ajHS-glycoprotein feH S ), haptoglobin (Hp), apolipoprotein B (ALpB), C5 component (C5) and antihemophilic fac tor (AHF) were demonstrated for the first time to be produced by the tumor studied.
Materials and Methods Tumor The yolk sac cell line, JTG-1, used in this study was established from the testicular tumor of a 27year-old male patient. It had been transplanted into
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
Introduction
185
Protein Production by Yolk Sac Tumor
a.AFP
C
Fig. 1. Results of double immunodiffusion tests for human plasma proteins in cystic fluid of the tumor in mouse B. The following abbreviations are employed besides those listed in table 1: HS = normal human serum; M = normal mouse serum; C = mouse cystic fluid. An ‘a.’ before any of the above terms indicates an antibody to that protein.
nude mice and maintained over 20 passages by subcu taneous inoculation [5]. Histological features of the tumor were those of typical yolk sac tumor [7] in show ing reticular, solid and endodermal sinus patterns [5], Hepatocellular differentiation [8, 9] was not seen. As the tumors grew, they formed a large cyst, the fluid of which contained human plasma proteins in much higher concentrations than are contained in plasma. Immunological Analyses The presence of human plasma proteins in the plasma and cystic fluid of nude mice was examined by double immunodiffusion [10] in 1% agarose gels in pH 8.6, 0.05 M barbital buffer. Antisera against a r acid glycoprotein, ci|AT, ALpA, ciiHS, a 2-macroglobulin, pregnancy-associated ai-glycoprotein, Hpx, Hp, RPB, AHF, prothrombin, pregnancy-specific Pi-gly coprotein, ALpB, and complement components C3a, C3c, C4, C lq, C9, C3, and C5 were obtained from Hoechst, FRG, and those against PA, Alb, ai-antichy-
motrypsin, Tf, ceruloplasmin, IgA, IgG, IgM and IgE were obtained from Dakopatts, Denmark. Antiserum against AFP was previously described [11]. Antisera were absorbed by adding 2 volumes of mouse serum to eliminate possible cross-reactivities to mouse pro teins. Antigens and antisera were appropriately di luted to obtain suitable antigen-antibody ratios. Lev els of human proteins were determined by single radial immunodiffusion [10] where commercially available antibody-containing gels (Hoechst) or those prepared during the investigation were employed.
Results The transplanted tumor grew forming a cyst, and 8 weeks after the transplantation, cystic fluid and plasma were obtained from 2 nude mice designated A and B. Up to 12 ml
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
AFP M ------- >
N ishi/N ishita/Ohka wa
186
Protein
Abbreviation
Prealbumin Albumin ai-Antitrypsin Apolipoprotein A1 Retinol-binding protein ctjHS-Glycoprotein Haptoglobin Hemopexin Apolipoprotein B Transferrin C5 component Antihemophilic factor a-Fetoprotein
PA Alb a,AT ALpA RBP a 2HS HP Hpx ALpB Tf C5 AHF AFP
o f cystic fluid was obtained from mouse A which had a 1.2-g solid tumor mass and 9 ml from mouse B having a 1.3-g tumor. Double immunodiffusion tests which em ployed 31 specific antisera showed the pres ence o f 13 proteins (table 1) in the cystic fluids o f the mice. Figure 1 shows that react ing cystic fluid proteins formed completely fused precipitin lines with normal human serum or purified proteins. Essentially, simi lar results were obtained with cystic fluids obtained from mouse A and B. Nine o f the 13 plasma proteins detected in cystic fluid were quantitated by single radial immunodiffusion (table 2). Levels of some o f the proteins in plasma were also determined (table 2).
Discussion Xenotransplantation o f human tumors into nude mice is a useful system for investi gating protein production by tumors, as pre viously demonstrated by Yoshimura et al.
Table 2. Quantitation of human plasma proteins in cystic fluid and plasma of mice bearing yolk sac tumor Proteins
Alb d|AT RBP CbHS Hp Hpx ALpB Tf AFP
Concentration pg/ml mouse A
mouse B
cystic fluid
plasma
cystic fluid
plasma
NT 2.2 NT NT NT NT ND 0.8 4.1
6.6 70.0 2.8 4.3 3.2
0.4 6.1 NT NT NT NT ND 3.5 5.3
0.3 8.0 0.3 0.9 0.9 0.4 10.5 6.0 31.2
1.0
90.0 40.0 58.0
NT = Not tested; ND = no measurable amount detected.
[4]. Data in table 2 show that the levels o f a given protein are usually much higher in cys tic fluid than in plasma. This may be due to the fact that human proteins secreted into the cyst are degraded more slowly than those in the circulation or undergo considerable dilution as they diffuse into serum. Avail ability of sufficient cystic fluid containing relatively high concentrations o f human pro teins makes it possible to systematically test human plasma protein production by the rel atively insensitive immunological tech niques used in this study. Cross-reactions were easily avoided by absorbing antisera with mouse serum. Levels o f plasma proteins in cystic fluid o f mouse B are higher than those of mouse A. This may reflect the fact that the tumor/cystic fluid ratio o f mouse B (1.3g/9m l) is higher than that o f mouse A (1.2 g /12 ml).
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Table 1. Abbreviations of plasma proteins
187
Protein Production by Yolk Sac Tumor
liver are also sites o f synthesis o f these pro teins [19], it is o f interest that two morpho logically very different tissues produce the same spectrum o f plasma proteins. This fact may indicate that an activating mechanism exists in common for these genes and is working in both tissues.
Acknowledgements This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, to SN. We are grateful to M. Takada for her excellent secretarial assistance.
References 1 Abelev GI, Assecritova IV, Kraevsky NA, Perova SD, Perevodchikova NI: Embryonal serum aglobulin in cancer patients: Diagnostic value. Int J Cancer 1967;2:551-558. 2 Shirai T, Itoh T, Yoshiki T, Noro T, Tomino Y, Hayasaka T: Immunofluorescent demonstration of alpha-fetoprotein and other plasma proteins in yolk sac tumor. Cancer 1976;38:1661-1667. 3 Sakashita S, Hirai H, Nishi S, Nakamura K, Tsuji I: a-Fetoprotein synthesis in tissue culture of hu man testicular tumors and an examination of ex perimental yolk sac tumors in the rat. Cancer Res 1976;36:4232-4237. 4 Yoshimura S, Tamaoki N, Ueyama Y, Hata J: Plasma protein production by hum an tum ors xe-
notransplanted in nude mice. Cancer Res 1978; 38:3474-3478. 5 Ohkawa K, Koike K, Amasaki H, Tohtake T, Nakata H, Dohsono H: Hetero-transplantation of human embryonal carcinoma into the nude mouse: Functional and morphologic examination. Asia Oceania J Obstet Gynaecol 1980;6:73-81. 6 Talerman A, Haije WG, Baggerman L: Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: Cor relation between endodermal sinus (yolk sac) tu mor and raised serum AFP. Cancer 1980;46:380385.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
In this study, the synthesis o f 13 human plasma proteins by yolk sac tumor JTG-1 was demonstrated. These tumors may simu late the functional manifestation o f their normal counterpart, the yolk sac. Human yolk sac has been reported to produce PA, Alb, ctiAT, T f and AFP by Gitlin et al. [12] and Shi et al. [13], ALpA by Shi et al. [13], and ALpB by Shi et al. [13] and Hopkins et al. [14], All o f these proteins were demon strated to be produced by the tumor em ployed in this study. Except for the synthesis o f RBP by rat yolk sac [15, 16], this protein and 012HS, Hp, Hpx, C5 and AHF have not been reported to be produced by human yolk sac or that o f other animals. The production o f Hpx by human yolk sac tumor as shown in the present study, has been reported by oth ers [4], The synthesis o f RBP by mouse em bryonal carcinoma cells which were differen tiated and contained visceral endoderm-like cells has also been reported [17]. At present, limited information is avail able on plasma protein production by hu man yolk sac because o f the difficulties in obtaining sufficient material at an early stage o f embryogenesis. This makes systematic ex aminations of such tissue difficult. Recently, cDNA probes for several plasma proteins have been used for the studies o f protein syn thesis by human yolk sac [14] and that of rodents [16-19], Since this technique is highly sensitive and specific, it will offer a powerful tool for the study o f protein synthe sis by human yolk sac as well as yolk sac tumors. Proteins found to be produced by yolk sac tumors suggest that they are most likely produced by normal yolk sac during embryogenesis. The absence o f hepatoid tis sues in yolk sac tumor JTG-1 suggests that plasma proteins are synthesized by yolk sac elements in the tumor. Since adult and fetal
7 Teilum G: Special tumors of ovary and testis. Comparative pathology and histological identifi cation, ed 2. Copenhagen, Lippincott, 1976. 8 Ulbright TM, Roth LM, Brodhecker CA: Yolk sac differentiation in germ cell tumors. Am J Surg Pathol 1986;10:151-164. 9 Nakashima N, Fukatsu T, Nagasaka T, Sobue M, Takeuchi J: The frequency and histology of he patic tissue in germ cell tumors. Am J Surg Pathol 1987;11:682-692. 10 Ouchterlony 6 , Nilsson LA: Immunodiffusion and immunoelectrophoresis; in Weir DM (ed): Handbook of Experimental Immunology, ed 2. Oxford, Blackwell Scientific Publications, 1978, pp 19.1-19.44. 11 Nishi S: Isolation and characterization of a hu man fetal a-globulin from the sera of fetuses and a hepatoma patient. Cancer Res 1970;30:25072513. 12 Gitlin D, Perricelli A: Synthesis of serum albu min, prealbumin, a-foetoprotein, ai-antitrypsin and transferrin by the human yolk sac. Nature 1970;228:995-997. 13 Shi WK, Hopkins B, Thompson S, Heath JK, Luke BM, Graham CF: Synthesis of apolipoproteins, alphafoetoprotein, albumin, and transferrin by the human foetal yolk sac and other foetal organs. J Embryol Exp Morph 1985;85:191-206. 14 Hopkins B, Brice AL, Schofield PN, Baralle FE, Graham CF: Identity of cells containing apolipoprotein B messenger RNA, in 6- to 12-week post fertilization human embryos. Development 1987; 100:83-93.
Nishi/Nishita/Ohkawa
15 Sklan D, Ross AC: Synthesis of retinol-binding protein and transthyretin in yolk sac and fetus in the rat. J Nutr 1987; 117:436-442. 16 Soprano DR, Wyatt ML, Dixon JL, Soprano KJ, Goodman DS: Retinol-binding protein synthesis and secretion by the rat visceral yolk sac. J Biol Chem 1988a;263:2934-2938. 17 Soprano DR, Soprano KJ, Wyatt ML, Goodman DS: Induction of the expression of retinol-binding protein and transthyretin in F9 embryonal carci noma cells differentiated to embryoid bodies. J Biol Chem 1988b;263:17897-17900. 18 Meehan RR, Barlow DP, Hill RE, Hogan BLM, Hastie ND: Pattern of serum protein gene expres sion in mouse visceral yolk sac and foetal liver. EMBO J 1984;3:1881-1885. 19 Schreiber G: Synthesis and secretion of plasma proteins; in Putnam FW (ed): The Plasma Pro teins, ed 2. Orlando, Academic Press, 1987, vol 5, pp 293-363.
Received: October 22, 1990 Accepted: January 28, 1991 Shinzo Nishi Department of Biochemistry Hokkaido University School of Medicine Sapporo 060 (Japan)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
188
Tumor Biol 1991 ; 12:184-188
Production of 13 Plasma Proteins by Human Testicular Yolk Sac Tumor Transplanted into Nude Mice Shinzo Nishi*, Toshiba Nishitah, Kiyoshi Ohkawac 3 Department of Biochemistry, Hokkaido University School of Medicine, Sapporo; b Department of Veterinary Physiology 1, Azabu University School of Veterinary, Sagamihara; cDepartment of Biochemistry, Jikei University School of Medicine, Tokyo, Japan
Key Words. Plasma protein • Yolk sac tumor • Nude mouse Abstract. Thirteen human proteins were found in plasma and cystic fluid o f mice bearing human testicular yolk sac tumor. Six o f them, a-fetoprotein, prealbumin, albumin, a [-anti trypsin, hemopexin and transferrin, had been previously demonstrated to be produced by yolk sac tumors. The syntheses o f the remaining seven, namely apolipoprotein A l, retinol binding protein, c^HS-glycoprotein, haptoglobin, apolipoprotein B, C5 component and anti hemophilic factor, have been demonstrated for the first time.
It is well established that human yolk sac tumors produce a-fetoprotein (AFP) [1-6] and several other plasma proteins [2-4], Us ing immunohistochemical techniques, Shirai et al. [2] showed that such tumors produced AFP, albumin (Alb), apantitrypsin (aiAT) and transferrin (Tf). We previously reported that testicular yolk sac tumor cultured with radiolabelled amino acid produced AFP, Alb and T f [3]. Immunoelectrophoretic analyses o f the plasma o f nude mice bearing yolk sac tumors demonstrated the synthesis o f preal bumin (PA) and hemopexin (Hpx) in addi tion to AFP, Alb, a|A T and T f [4], In the present study, we explored the production o f
plasma proteins by human testicular yolk sac tumor serially transplanted into nude mice using antisera against 31 human plasma pro teins. Seven o f 13 proteins detected, namely apolipoprotein A l (ALpA), retinol-binding protein (RBP), ajHS-glycoprotein feH S ), haptoglobin (Hp), apolipoprotein B (ALpB), C5 component (C5) and antihemophilic fac tor (AHF) were demonstrated for the first time to be produced by the tumor studied.
Materials and Methods Tumor The yolk sac cell line, JTG-1, used in this study was established from the testicular tumor of a 27year-old male patient. It had been transplanted into
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
Introduction
185
Protein Production by Yolk Sac Tumor
a.AFP
C
Fig. 1. Results of double immunodiffusion tests for human plasma proteins in cystic fluid of the tumor in mouse B. The following abbreviations are employed besides those listed in table 1: HS = normal human serum; M = normal mouse serum; C = mouse cystic fluid. An ‘a.’ before any of the above terms indicates an antibody to that protein.
nude mice and maintained over 20 passages by subcu taneous inoculation [5]. Histological features of the tumor were those of typical yolk sac tumor [7] in show ing reticular, solid and endodermal sinus patterns [5], Hepatocellular differentiation [8, 9] was not seen. As the tumors grew, they formed a large cyst, the fluid of which contained human plasma proteins in much higher concentrations than are contained in plasma. Immunological Analyses The presence of human plasma proteins in the plasma and cystic fluid of nude mice was examined by double immunodiffusion [10] in 1% agarose gels in pH 8.6, 0.05 M barbital buffer. Antisera against a r acid glycoprotein, ci|AT, ALpA, ciiHS, a 2-macroglobulin, pregnancy-associated ai-glycoprotein, Hpx, Hp, RPB, AHF, prothrombin, pregnancy-specific Pi-gly coprotein, ALpB, and complement components C3a, C3c, C4, C lq, C9, C3, and C5 were obtained from Hoechst, FRG, and those against PA, Alb, ai-antichy-
motrypsin, Tf, ceruloplasmin, IgA, IgG, IgM and IgE were obtained from Dakopatts, Denmark. Antiserum against AFP was previously described [11]. Antisera were absorbed by adding 2 volumes of mouse serum to eliminate possible cross-reactivities to mouse pro teins. Antigens and antisera were appropriately di luted to obtain suitable antigen-antibody ratios. Lev els of human proteins were determined by single radial immunodiffusion [10] where commercially available antibody-containing gels (Hoechst) or those prepared during the investigation were employed.
Results The transplanted tumor grew forming a cyst, and 8 weeks after the transplantation, cystic fluid and plasma were obtained from 2 nude mice designated A and B. Up to 12 ml
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
AFP M ------- >
N ishi/N ishita/Ohka wa
186
Protein
Abbreviation
Prealbumin Albumin ai-Antitrypsin Apolipoprotein A1 Retinol-binding protein ctjHS-Glycoprotein Haptoglobin Hemopexin Apolipoprotein B Transferrin C5 component Antihemophilic factor a-Fetoprotein
PA Alb a,AT ALpA RBP a 2HS HP Hpx ALpB Tf C5 AHF AFP
o f cystic fluid was obtained from mouse A which had a 1.2-g solid tumor mass and 9 ml from mouse B having a 1.3-g tumor. Double immunodiffusion tests which em ployed 31 specific antisera showed the pres ence o f 13 proteins (table 1) in the cystic fluids o f the mice. Figure 1 shows that react ing cystic fluid proteins formed completely fused precipitin lines with normal human serum or purified proteins. Essentially, simi lar results were obtained with cystic fluids obtained from mouse A and B. Nine o f the 13 plasma proteins detected in cystic fluid were quantitated by single radial immunodiffusion (table 2). Levels of some o f the proteins in plasma were also determined (table 2).
Discussion Xenotransplantation o f human tumors into nude mice is a useful system for investi gating protein production by tumors, as pre viously demonstrated by Yoshimura et al.
Table 2. Quantitation of human plasma proteins in cystic fluid and plasma of mice bearing yolk sac tumor Proteins
Alb d|AT RBP CbHS Hp Hpx ALpB Tf AFP
Concentration pg/ml mouse A
mouse B
cystic fluid
plasma
cystic fluid
plasma
NT 2.2 NT NT NT NT ND 0.8 4.1
6.6 70.0 2.8 4.3 3.2
0.4 6.1 NT NT NT NT ND 3.5 5.3
0.3 8.0 0.3 0.9 0.9 0.4 10.5 6.0 31.2
1.0
90.0 40.0 58.0
NT = Not tested; ND = no measurable amount detected.
[4]. Data in table 2 show that the levels o f a given protein are usually much higher in cys tic fluid than in plasma. This may be due to the fact that human proteins secreted into the cyst are degraded more slowly than those in the circulation or undergo considerable dilution as they diffuse into serum. Avail ability of sufficient cystic fluid containing relatively high concentrations o f human pro teins makes it possible to systematically test human plasma protein production by the rel atively insensitive immunological tech niques used in this study. Cross-reactions were easily avoided by absorbing antisera with mouse serum. Levels o f plasma proteins in cystic fluid o f mouse B are higher than those of mouse A. This may reflect the fact that the tumor/cystic fluid ratio o f mouse B (1.3g/9m l) is higher than that o f mouse A (1.2 g /12 ml).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
Table 1. Abbreviations of plasma proteins
187
Protein Production by Yolk Sac Tumor
liver are also sites o f synthesis o f these pro teins [19], it is o f interest that two morpho logically very different tissues produce the same spectrum o f plasma proteins. This fact may indicate that an activating mechanism exists in common for these genes and is working in both tissues.
Acknowledgements This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan, to SN. We are grateful to M. Takada for her excellent secretarial assistance.
References 1 Abelev GI, Assecritova IV, Kraevsky NA, Perova SD, Perevodchikova NI: Embryonal serum aglobulin in cancer patients: Diagnostic value. Int J Cancer 1967;2:551-558. 2 Shirai T, Itoh T, Yoshiki T, Noro T, Tomino Y, Hayasaka T: Immunofluorescent demonstration of alpha-fetoprotein and other plasma proteins in yolk sac tumor. Cancer 1976;38:1661-1667. 3 Sakashita S, Hirai H, Nishi S, Nakamura K, Tsuji I: a-Fetoprotein synthesis in tissue culture of hu man testicular tumors and an examination of ex perimental yolk sac tumors in the rat. Cancer Res 1976;36:4232-4237. 4 Yoshimura S, Tamaoki N, Ueyama Y, Hata J: Plasma protein production by hum an tum ors xe-
notransplanted in nude mice. Cancer Res 1978; 38:3474-3478. 5 Ohkawa K, Koike K, Amasaki H, Tohtake T, Nakata H, Dohsono H: Hetero-transplantation of human embryonal carcinoma into the nude mouse: Functional and morphologic examination. Asia Oceania J Obstet Gynaecol 1980;6:73-81. 6 Talerman A, Haije WG, Baggerman L: Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: Cor relation between endodermal sinus (yolk sac) tu mor and raised serum AFP. Cancer 1980;46:380385.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
In this study, the synthesis o f 13 human plasma proteins by yolk sac tumor JTG-1 was demonstrated. These tumors may simu late the functional manifestation o f their normal counterpart, the yolk sac. Human yolk sac has been reported to produce PA, Alb, ctiAT, T f and AFP by Gitlin et al. [12] and Shi et al. [13], ALpA by Shi et al. [13], and ALpB by Shi et al. [13] and Hopkins et al. [14], All o f these proteins were demon strated to be produced by the tumor em ployed in this study. Except for the synthesis o f RBP by rat yolk sac [15, 16], this protein and 012HS, Hp, Hpx, C5 and AHF have not been reported to be produced by human yolk sac or that o f other animals. The production o f Hpx by human yolk sac tumor as shown in the present study, has been reported by oth ers [4], The synthesis o f RBP by mouse em bryonal carcinoma cells which were differen tiated and contained visceral endoderm-like cells has also been reported [17]. At present, limited information is avail able on plasma protein production by hu man yolk sac because o f the difficulties in obtaining sufficient material at an early stage o f embryogenesis. This makes systematic ex aminations of such tissue difficult. Recently, cDNA probes for several plasma proteins have been used for the studies o f protein syn thesis by human yolk sac [14] and that of rodents [16-19], Since this technique is highly sensitive and specific, it will offer a powerful tool for the study o f protein synthe sis by human yolk sac as well as yolk sac tumors. Proteins found to be produced by yolk sac tumors suggest that they are most likely produced by normal yolk sac during embryogenesis. The absence o f hepatoid tis sues in yolk sac tumor JTG-1 suggests that plasma proteins are synthesized by yolk sac elements in the tumor. Since adult and fetal
7 Teilum G: Special tumors of ovary and testis. Comparative pathology and histological identifi cation, ed 2. Copenhagen, Lippincott, 1976. 8 Ulbright TM, Roth LM, Brodhecker CA: Yolk sac differentiation in germ cell tumors. Am J Surg Pathol 1986;10:151-164. 9 Nakashima N, Fukatsu T, Nagasaka T, Sobue M, Takeuchi J: The frequency and histology of he patic tissue in germ cell tumors. Am J Surg Pathol 1987;11:682-692. 10 Ouchterlony 6 , Nilsson LA: Immunodiffusion and immunoelectrophoresis; in Weir DM (ed): Handbook of Experimental Immunology, ed 2. Oxford, Blackwell Scientific Publications, 1978, pp 19.1-19.44. 11 Nishi S: Isolation and characterization of a hu man fetal a-globulin from the sera of fetuses and a hepatoma patient. Cancer Res 1970;30:25072513. 12 Gitlin D, Perricelli A: Synthesis of serum albu min, prealbumin, a-foetoprotein, ai-antitrypsin and transferrin by the human yolk sac. Nature 1970;228:995-997. 13 Shi WK, Hopkins B, Thompson S, Heath JK, Luke BM, Graham CF: Synthesis of apolipoproteins, alphafoetoprotein, albumin, and transferrin by the human foetal yolk sac and other foetal organs. J Embryol Exp Morph 1985;85:191-206. 14 Hopkins B, Brice AL, Schofield PN, Baralle FE, Graham CF: Identity of cells containing apolipoprotein B messenger RNA, in 6- to 12-week post fertilization human embryos. Development 1987; 100:83-93.
Nishi/Nishita/Ohkawa
15 Sklan D, Ross AC: Synthesis of retinol-binding protein and transthyretin in yolk sac and fetus in the rat. J Nutr 1987; 117:436-442. 16 Soprano DR, Wyatt ML, Dixon JL, Soprano KJ, Goodman DS: Retinol-binding protein synthesis and secretion by the rat visceral yolk sac. J Biol Chem 1988a;263:2934-2938. 17 Soprano DR, Soprano KJ, Wyatt ML, Goodman DS: Induction of the expression of retinol-binding protein and transthyretin in F9 embryonal carci noma cells differentiated to embryoid bodies. J Biol Chem 1988b;263:17897-17900. 18 Meehan RR, Barlow DP, Hill RE, Hogan BLM, Hastie ND: Pattern of serum protein gene expres sion in mouse visceral yolk sac and foetal liver. EMBO J 1984;3:1881-1885. 19 Schreiber G: Synthesis and secretion of plasma proteins; in Putnam FW (ed): The Plasma Pro teins, ed 2. Orlando, Academic Press, 1987, vol 5, pp 293-363.
Received: October 22, 1990 Accepted: January 28, 1991 Shinzo Nishi Department of Biochemistry Hokkaido University School of Medicine Sapporo 060 (Japan)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 9:07:18 PM
188
