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.
Nomura
T
T
Department of Radiation Biology, Osaka University.
Takahama
Y
Y
Hongyo
T
T
Takatera
H
H
Inohara
H
H
Fukushima
H
H
Ono
S
S
Hamaoka
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D003433:Crosses, Genetic; D004407:Dysgerminoma / Q000276:immunology / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008649:Mesonephroma / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D013736:Testicular Neoplasms / Q000276:immunology / Q000473:pathology*; D014183:Transplantation, Heterologous; D014594:Uterine Neoplasms / Q000276:immunology / Q000473:pathology*