Establishment of highly metastatic human tumor cell line in nude mice

A total of 22 adult nude mice (7 approximately 17 weeks old) of BALB/cA origin were inoculated subcutaneously (SC) with human tumor cell lines derived from rhabdomyosarcoma and lung carcinomas, including squamous cell carcinoma, bronchiolo-alveolar carcinoma, small cell carcinoma, giant cell carcinoma and 2 types of adenocarcinoma. 12 neoplasms (54.5%) was confirmed at the initial transplantation and 7 serially transplantable tumors were established in 201 nude mice. Metastatic behavior of 7 human tumor cell lines grown in nude mice was judged histologically after sacrifice and SC transplanted tumors could either be highly metastatic (giant cell carcinoma), moderately metastatic (adenocarcinoma PAb), poorly metastatic (squamous cell carcinoma and adenocarcinoma PAa) or non-metastatic (small cell carcinoma and bronchiolo-alveolar carcinoma). The tumor from SC inoculated giant cell carcinoma (PG) could produce regional and/or distant lymph node metastases (12/12) and lung metastases (9/12) in BALB/cA nude mice maintained under semi-barrier system conditions. Six NIH nude mice developed metastatic tumor nodules both in the lymph node and lung (6/6) under the same condition. The highly metastasizing property of PG transplanted tumors remained after passage for as many as 18 times. The limitations of nude mice as an in vivo model for the study of tumor biology are discussed, eg. malignant neoplasms rarely metastasize when transplanted into nude mice. The use of such model (PG) could lead to a better understanding of the biology of metastasis, thus contributing to the development of new approaches to the therapy of metastasis.     

Transplantation of human basal cell carcinoma to C57/BALB/C bgJ/bgJ-nu/nu (beige-nude) mouse

The purpose of this study was to evaluate the transplantation of BCC to the C57/BALB/C bgJ/bgJ-nu/nu (beige-nude) mouse. This animal has two gene defects which are expressed as impairment of natural killer cells (NK cells) as well as the absence of a thymus. The results demonstrate that human BCC can be successfully transplanted to the C57 beige-nude mouse without the need for supplemental immunosuppression. It may be that the impairment of NK cell activity in the beige-nude mouse model plays a significant role in tumor transplantation.     

Environmental and genetic factors determine the level of NK activity of nude mice and affect their suitability as models for experimental metastasis

In these studies we have evaluated the effects of age, genetic background, and housing conditions on the NK-cell activity of nude mice measured in vitro and resistance to tumor metastasis in vivo. BALB/cAnN nude mice exhibited lower levels of NK-cell-mediated cytotoxicity than age-matched N:NIH(S) nude mice maintained under similar housing conditions. The stronger response of N:NIH(S) nude mice was observed also after experimental activation of NK cells by Corynebacterium parvum. Nude mice maintained under barrier conditions have weaker NK-cell activity than mice maintained under conventional conditions. The incidence of experimental pulmonary metastases of allogeneic tumors injected into nude mice was inversely correlated with the levels of NK-cell-mediated cytotoxicity. Thus, 3-week-old BALB/cAnN nude mice raised under barrier conditions were more sensitive to development of experimental metastasis than age-matched N:NIH(S) nude mice maintained under barrier conditions or nude mice of either strain maintained under conventional conditions. In both strains, however, the relative differences in metastatic potential among the tumor cell lines observed in syngeneic recipients were maintained. We conclude that young BALB/cAnN nude mice raised under barrier conditions may provide a valuable in vivo model for studying metastasis of neoplasms.     

Role of natural killer cells in control of cancer metastasis

Summary There is a close association between levels of natural killer (NK) cell activity and the ability of the host to eliminate circulating tumor cell emboli. Mice that exhibit low levels of NK-cell-mediated cytotoxicity (3-week-old syngeneic mice, 3-week-old allogeneic nude mice, cyclophosphamide- or -estradiol-treated mice, and beige mice) also exhibit enhanced survival of tumor cells in the vascular bed of the lung and increased incidence of pulmonary tumor metastasis. Conversely, hosts with high NK cell activity (adult nude mice and syngeneic mice treated with NK-cell-stimulating biological response modifiers (BRM)) are very resistant to metastasis. Lymphoid adoptive transfer studies have shown that the effector cell responsible for the antimetastatic activity is the NK cell. In these studies, NK cells were highly effective in destroying circulating tumor cells before their extravasation into the organ parenchyma, whereas they exerted only a minimal inhibiting effect on already established micrometastases. The ability to activate NK cells selectively (without subsequently inducing suppressor macrophages) provides a valuable tool for the evaluation of the role of activated NK cells in therapy of tumor metastasis. The validity of this approach is supported by the finding that NK cells activated by BRM are effective in killing, both in vivo and in vitro, solid tumor cells that developed NK-cell-resistance as a result of adaptive growth in vivo or selection during the metastatic process. An understanding of the mechanisms that regulate NK cell activation or suppression as well as elucidation of the circulatory patterns and anatomical compartmentalization of activated NK cells will help achieve a sustained systemic and/or in situ activation of NK cells which may prove effective in the control of cancer metastasis.     

基质降解酶u-PA,PAI-1与人肺癌细胞浸润转移的相关关系的研究

观察体外细胞株ＰＧ、ＰＡａ细胞的ｕ－ＰＡ，ＰＡＩ－１活性和抗原表达，结果发现ＰＧ、ＰＡａ细胞均能够产生ＰＡ及ＰＡＩ，免疫细胞化学法定位ＰＡ主要为ｕ－ＰＡ，ＰＡＩ主要为ＰＡＩ－１。在ＰＧ为ｕ－ＰＡ高表达，而ＰＡａ为低ｕ－ＰＡ表达，ＰＡＩ－１在ＰＧ、ＰＡａ细胞中均高表达。对ＰＧ瘤细胞在ＢＡＬＢ／ＣＡ裸鼠皮下种植性瘤组织的免疫组化结果显示，ｕ－ＰＡ阳性～强阳性表达，ＰＡＩ－１为阴性表达。说明ｕ－ＰＡ是ＰＧ、ＰＡａ高低不同的转移能力的重要机制之一。     

Invasion and metastasis of SY86B human gastric carcinoma cells in nude mice

A moderately differentiated tubular adenocarcinoma of human stomach, named SY86B, was successfully transplanted subcutaneously to nude mice of different genetic backgrounds (BALB/CA/PBI-nu, C57BL/6J.615/PBI-nu and ICR.BALB/CA/PBI-nu). The tumor has been passaged for 13 generations and the transplantability was 100%. The SY86B cells retained the capacity of invasive and metastatic growth in the nude mice and showed a high rate of metastasis to the regional lymph nodes and to such distant organs as the lungs, liver and pancreas. The overall rate of metastasis was 77.7%. The species of the nude mice, their age and sex apparently did not significantly affect the occurrence of metastasis. Tumor-bearing time and the aggressive character of the tumor cells themselves appeared important for the genesis of metastasis. This experimental model can provide a new approach to basic and clinical studies of cancer metastasis.     

Evaluation of role of natural killer cells in radiation-induced leukemogenesis in mice

The relationship of the leukemogenic and natural killer (NK)-suppressive effects of fractionated doses of gamma-radiation in mice was studied. A/J mice were relatively resistant; CBA/J, BALB/c, and C57BL/6 were susceptible to both the NK-suppressive and leukemogenic effects, and young (1 mo old) C57BL/6 mice were more susceptible than were 2- and 3-month-old C57BL/6 mice to both effects. Age-dependent susceptibility to radiation-induced leukemogenesis also was observed in C57BL/6 (bg/bg) (beige) mice. No differences in incidence and latent period of lymphoma development were found between C57BL/6 (+/+) and beige mice. Bone marrow cells (BMC) from normal C57BL/6 donors reconstituted the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients and inhibited leukemogenesis. Although BMC of beige donors did not reconstitute the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients, these cells were as efficient for antileukemic protection as were BMC from C57BL/6 (+/+) mice. The bone marrow of irradiated mice contained preleukemia cells that produced leukemias when transplanted iv into recipients preirradiated with 400 R. Inoculation (iv) of spleen cells (SpC) from syngeneic nude mice plus preleukemia bone marrow cells (PBMC) were able to inhibit leukemia formation in the 400 R-irradiated recipients. SpC from beige mice, normal C57BL/6 (+/+) mice, or C57BL/6 (+/+) mice treated with anti-asialo GM1 serum had no influence on the development of leukemia after their transplantation with PBMC.     

ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。     

Invasion and Metastasis of SY86B Human Gastric Carcinoma Cells in Nude Mice

A moderately differentiated tubular adenocarcinoma of human stomach, named SY86B, was successfully transplanted subcutaneously to nude mice of different genetic backgrounds (BALB/CA/PBI- nu , C57BL/6J.615/PBI- nu and ICR-BALB/CA/PBI- nu ). The tumor has been passaged for 13 generations and the transplantability was 100%. The SY86B cells retained the capacity of invasive and metastatic growth in the nude mice and showed a high rate of metastasis to the regional lymph nodes and to such distant organs as the lungs, liver and pancreas. The overall rate of metastasis was 77.7%. The species of the nude mice, their age and sex apparently did not significantly affect the occurrence of metastasis. Tumor-bearing time and the aggressive character of the tumor cells themselves appeared important for the genesis of metastasis. This experimental model can provide a new approach to basic and clinical studies of cancer metastasis.     

Enhanced metastases of a mouse carcinoma after in vitro treatment with murine interferon gamma

We have studied the influence of interferons (IFNs) on the metastatic potential of mouse colon adenocarcinoma, COLON 26, cells. Pre-treatment of the cells in vitro for 24 hr with recombinant murine IFN-gamma (rMuIFN-gamma) significantly increased the number of lung tumour nodules when cells were injected i.v. into immunocompetent BALB/c mice and BALB/c nude mice. However, when MuIFN-gamma-pre-treated cells were injected into beige (NK-deficient) nude mice or anti-asialoGM 1 (asGM 1)-serum-treated BALB/c mice (NK-depleted) no enhancement of metastatic potential was seen. Pre-treatment of COLON 26 cells with recombinant human IFN-alpha A/D (Bg1 I), an IFN with equal activity on human and mouse cells, did not significantly enhance their subsequent metastases in immunocompetent or immunodeficient mice. In fact, there was a small but significant decrease in the number of tumour nodules in the lungs of beige nude and asGM 1-treated mice. The effects of rMuIFN-gamma on COLON 26 cells did not appear to be related to an alteration in MHC expression. COLON 26 cells constitutively express H-2D and H-2K antigens and both IFNs had equal enhancing (approx. 2-fold) activity on the expression of these antigens at the doses used in this experiment (10(3)U/ml). We conclude that pre-treatment with rMuIFN-gamma renders COLON 26 cells resistant to in vivo NK-cell lysis via a mechanism that does not involve changes in MHC expression.     

Establishment of Nude Mice Lacking NK Cells and Their Application for Human Tumor Xenografts

Objective: Nude mice are used as a recipient for human tumor cell xenografts. However, the success rate of xenotransplantation is unsatisfactory due to high natural killer (NK) activity. To overcome this limitation, we established nude mice with no NK cells, and compared the transplantation efficiency with that in nude mice. Methods: BALB/c Nude Jak3-/- (Nude-J) mice were established by crossing BALB/c Nude mice and BALB/c Jak-3-/- mice. Hematopoietic malignant cell lines (BCBL-1 and Z138) were implanted subcutaneously to compare the tumorigenicity in Nude-J mice with Nude Rag-2/Jak3 double deficient (Nude RJ) mice and nude mice. Results: Nude-J mice showed complete loss of NK and T lymphocytes, whereas B lymphocytes remained. Both BCBL-1 and Z138 human lymphoid malignant cell lines formed almost the same sizes of subcutaneous tumors in Nude-J and Nude RJ mice, whereas they formed no or only small tumors in nude mice. Splenocytes from Nude-J mice showed no cytotoxic activity in vitro. Conclusion: Nude-J mice can be a valuable tool for human tumor cell transplantation studies.     

Metastatic characteristics of SY86B human gastric carcinoma in athymic nude mice

The invasive and metastatic behavior of SY86B human gastric carcinoma in nude mice were further studied. The results showed that this human cancer strain had a relatively high spontaneous metastatic rate (68.4%). The metastasis was related to the invasiveness of the transplanted tumor and tumor-bearing time. Since the metastasis developed from 2nd to 9th passages, it was considered that this model had a stable metastatic tendency. It was observed that the genetic background, age and sex difference of the recipient nude mice may not be associated with the metastasis. Aside from the high transplantable rate (100%) and spontaneous metastatic rate (68.4%), SY86B human gastric carcinoma strain still maintains the morphologic, immunologic, genetic and ultrastructural characteristics of the original tumor. All these make it a useful means in the study of diagnosis and treatment of cancer metastasis.     

Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity

Of 6- and 3-week-old nude mice given intravenous injections of murine tumor cells with well-defined metastatic properties, only the 3-week-old mice developed lung tumor colonies in significant numbers. The quantitative differences in metastatic potential among tumor cell lines injected into syngeneic recipients were also maintained following intravenous injection into young nude mice. Successful metastasis in 3-week-old nude mice is correlated with the low levels of natural killer cell activity detected in these young recipients. Boosting of the natural killer cell activity of 3-week-old nude mice by the administration of bacterial adjuvants and interferon inducers significantly inhibited metastasis formation. The differences in metastasis development could not be attributed to differences in the initial arrest of tumor cells in the pulmonary vascular bed, but rather to a better survival of the arrested cells in the lungs of 3-week-old nude mice as compared with 6-week-old counterparts. We conclude that low levels of NK cell activity are associated with increased incidence of experimental metastasis.     

Cdx2过表达对裸鼠人胃癌移植瘤生长和转移的影响

目的观察Cdx2基因过表达对裸鼠人胃癌移植瘤生长和转移的影响。方法利用脂质体将pCMV-Cdx2-HA质粒或pCMV-HA质粒分别转染人胃癌MGC-803细胞,命名为MGC-803/Cdx2细胞或MGC-803/EV细胞。将两种细胞分别注射入裸鼠近腋右背侧皮下,待皮下成瘤后将瘤组织接种于胃,建立裸鼠人胃癌移植瘤模型：接种MGC-803/Cdx2皮下瘤的裸鼠为实验组,接种MGC-803/EV皮下瘤的裸鼠为对照组;30 d后处死裸鼠,观察移植瘤生长、转移情况,并应用半定量逆转录-聚合酶链反应(RT-PCR）和Western blot技术检测移植瘤中Cdx2 mRNA和蛋白的表达。结果实验组肿瘤体积为(13.42±2.34）mm3,明显低于对照组的肿瘤体积(17.59±2.80）mm3(P<0.05）;实验组成瘤率(73.3%）低于对照组成瘤率(86.7%）;两组肿瘤转移情况比较,差异无统计学意义(P>0.05）;实验组肿瘤组织Cdx2 mRNA和蛋白表达明显增加(P<0.05）。结论 Cdx2过表达抑制裸鼠人胃癌移植瘤的生长,但对肿瘤转移无明显影响。     

Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts,and subcutaneous or intravenous injection routes

We have examined two features of neuroblastoma cells that had not been well-characterized in a xenogeneic model: The cells display unusual immunologic properties in other experimental systems, and the original tumors display widespread and characteristic patterns of metastasis. To determine the most appropriate immunodeficient host for primary tumor growth, T cell-deficient nude mice, NK-deficient beige mice, beige-nudes, and controls were injected with the well-characterized line CHP-100. To define the pattern of tumor spread, complete autopsies were performed following subcutaneous, intraperitoneal and intravenous injections. CHP-100 consistently formed subcutaneous tumors in T cell-deficient mice (nude and beige-nude), but not in T cell-competent mice (beige, heterozygous nu/+ and bg/+, or wild-type). The growth rate and final size of the subcutaneous tumors were not greater in beige-nudes than in nudes. All mice showed early CHP-100 cell death after subcutaneous injection; the nature of the immunodeficiency was more relevant for the surviving subpopulation. Widespread dissemination was seen following intravenous injection, particularly in beige-nudes. Aspects of the growth patterns were appropriate to the tumor of origin. The behavior in immunodeficient mice suggests that T cells can play a role in controlling the growth of these cells; the next steps will be to define the effector mechanisms, and to determine if they can be exploited for human patients. The hematogenous spread following intravenous injection suggests that insights into the control of blood-borne tumor may also come from further study of this model.     

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

The type I insulin-like growth factor receptor (IGF-IR) plays an important role in the growth and transformation of breast cancer cells. In this study, we investigated the effects of treatment with an antisense IGF-IR construct on cells from the highly metastatic estrogen receptor-negative human breast cancer cell line MDA-MB-435s. The cells carrying the antisense IGF-IR had a markedly reduced expression of IGF-IR, had a significant decrease in cell proliferation, and lost the ability to form colonies in soft agar. There was a delay in tumor formation and a dramatic reduction in tumor size when cells carrying the antisense IGF-IR were injected into either nude or severe combined immunodeficient (scid) beige mice. We have also provided data that show that the scid beige mouse is a more suitable model for studying metastasis of the MDA-MB-435s cells. All of the scid beige mice injected with cells carrying the control construct had metastasis to the lungs, whereas lungs from the nude mice had no apparent metastatic sites after 11 weeks. When cells carrying antisense IGF-IR were injected subcutaneously in scid beige mice, the animals had a significant increase in survival compared with mice injected with cells carrying the control construct. Taken together, these results indicate that the IGF-IR can play a critical role in the progression of breast cancer. Our studies provide a basis for the development of future treatment strategies targeting the IGF-IR in metastatic breast cancer.     

人原发性小肠恶性黑色素瘤裸鼠原位移植高转移模型的建立

目的 建立人原发性小肠恶性黑色素瘤裸小鼠原位移植高转移模型.方法 将手术切除的人原发性小肠恶性黑色素瘤原发灶和肝转移灶新鲜瘤组织块分别植入裸鼠小肠黏膜层内,观察原位移植的成瘤率、移植瘤的侵袭性和转移率,并进行形态学、流式细胞分析和染色体核型分析.结果 人小肠恶性黑色素瘤原发灶和肝转移灶新鲜组织均移植成功,建成人原发性小肠(原发灶)恶性黑色素瘤裸鼠原位移植高转移模型(ttSIM-0602)和人原发性小肠(肝转移灶)恶性黑色素瘤裸鼠原位移植肝转移模型(HSIM-0603).HSIM4)602和HSIM-0603模型分别传至21代和23代,共移植裸鼠227只,其肿瘤移植生长率和液氮冻存复苏成活率均为100%.HSIM-0602模型肝转移率为65.7%,肺转移率为84.8%,淋巴结转移率为63.8%.HSIM-0603模型肝转移率为100%,肺转移率为46.7%,淋巴结转移率为71.3%.移植瘤组织病理学为小肠高度恶性黑色素瘤.免疫组织化学显示,S-100蛋白和HMB-45均为阳性表达.电镜下,瘤细胞浆内可见大量的黑色素小体,也可见黑色素复合体.HSIM-0602模型移植瘤细胞DNA指数为1.59±0.07,HSIM-0603模型移植瘤细胞DNA指数为1.71±0.12,均为异倍体.染色体核型分析显示,HSIM-0602模型移植瘤细胞染色体数为55～57条,HSIM-0603模型移植瘤细胞染色体数为57～59条.结论 HSIM-0602和HSIM-0603模型是成功的人原发性小肠恶性黑色素瘤裸鼠原位移植自发性高转移模型,完整地模拟了人原发性小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤转移生物学和抗转移治疗提供了理想的动物模型.     

采用OB胶粘贴法建立人胃癌裸鼠原位种植转移模型

背景与目的建立理想的动物肿瘤移植模型是进行肿瘤防治研究的重要前提,目前公认的胃癌造模的方法为采用完整组织块的“皮下移植法”、“胃囊法”,但传统的造模方法目前尚存在操作复杂、成活率低等缺点,本研究拟采用“OB胶粘贴法”更简便地建立人胃癌裸鼠原位移植模型。方法以反复接种传代于裸鼠皮下的SGC鄄7901人胃癌细胞株建立的移植瘤组织块为材料,将其用生物吻合“OB胶”原位粘贴于裸鼠胃壁,并与传统“胃囊法”、“皮下移植法”比较观察移植肿瘤的生长情况、移植成功率和自发转移的发生率。结果“OB胶粘贴法”组原位移植成功率为100%,局部淋巴结转移率为100%,肺转移发生率为62.5%,肝转移发生率为87.5%,腹膜转移发生率为87.5%,较之胃囊法(分别为100%、100%、50.0%、50.0%和33.3%),除腹膜转移率升高外,远处脏器转移差异无显著性,但成活率高。皮下移植组未发生局部浸润及远处转移。结论“OB胶粘贴法"能更简便地建立人胃癌高转移模型,重现临床转移过程。     

Interferon-induced alterations in metastatic capacity, class-1 antigen expression and natural killer cell sensitivity of melanoma cells

Pre-treatment of B16 melanoma cells with recombinant interferon-gamma (IFN-gamma) markedly increased their lung-colonising capacity following i.v. injection into syngeneic mice as compared with control cells. A similar enhancement was observed following the injection of treated cells into athymic nude mice but not in athymic mice carrying the beige mutation. Pre-treatment of syngeneic mice with anti-asialo GM1 antibody effectively abrogated any interferon-induced increase in experimental metastatic activity. The same IFN-gamma treatment significantly increased resistance of B16 cells to splenic natural killer (NK) cell activity as determined by in vitro assays. IFN-alpha/beta pre-treatment of B16 cells decreased sensitivity to NK-cell-mediated lysis to a lesser extent than IFN-gamma and had no detectable effect upon the subsequent metastatic activity of the tumor cells. Class-I antigen expression was altered by these IFN treatments, with IFN-gamma causing dramatic increases in expression of H-2Db antigen, in a pattern consistent with the possibility that increased H-2 antigen expression on B16 cells led to decreased NK-cell sensitivity which was reflected by an increase in experimental metastatic capacity.     

Rapid growth and spontaneous metastasis of human germinal tumors ectopically transplanted into scid (severe combined immunodeficiency) and scid-nudestreaker mice

Xenograft acceptance, growth and spontaneous metastasis of ectopically transplanted human germinal tumors were compared among scid mice, athymic nude mice and F2 hybrids constructed from scid and nude mice, in relation to the impairments of T and B cell functions in these mice. In scid mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) that originated from the ovary grew to enormous sizes in 100% of the animals after both subcutaneous and intraperitoneal transplantation, while only half (59.1% and 51.9%) of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice (BALB/c-nu/nu and CD1-nu/nu). The YST-2 grew rapidly in scid mice, developing 3 to 10 times larger tumors compared to nude-streaker (AKR/J-nustr/nustr) and usual nude mice, respectively. Furthermore, ectopically transplanted tumors spontaneously metastasized to distant organs (mostly to the lung) in scid mice (but less frequently in leaky scid mice), while metastases have never been found in nude mice. Although a xenograft of human classic (typical or pure) seminoma of the testis has never been established in nude mice, it grows slowly in one-third (36.4%) of scid mice and very rapidly in all of scid-nustr (scid/scid; nustr/nustr) double mutant mice. Spontaneous metastases of xenografted seminomas were also observed in distant organs (lymph node, lung, liver, spleen, and kidney). The metastastic distribution of the two human germinal tumors in scid and scid-nustr mice mimics that found in human. These results (xenograft acceptance, growth of transplanted tumors and degree of metastatic spread) were compatible with the level of T and B cell impairments indicated by FACS analysis, as well as mitogen responses, serum IgG and morphological features of the thymus.