An Antigen in Hodgkin's Disease Tissue Cultures: Radioiodine-Labeled Antibody Studies

Long, John C.; Aisenberg, Alan C.; Zamecnik, Paul C.

doi:10.1073/pnas.71.7.2605

Proc. Natl. Acad. Sci. U.S.A.

1974

DOI: 10.1073/pnas.71.7.2605

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An Antigen in Hodgkin's Disease Tissue Cultures: Radioiodine-Labeled Antibody Studies

John C. Long¹,

Alan C. Aisenberg²,

Paul C. Zamecnik³

Abstract: An antiserum was prepared in rabbits against an antigen obtained by density gradient

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1975

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Cited by 7 publications

(2 citation statements)

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“…In earlier work long-term monolayer cell cultures were prepared from Hodgkin's disease tumors in the spleen (1). Cells from these monolayers contained an antigen on the surface and within the cytoplasm that could be isolated and purified from supernatant medium (2,3). The antigen was not demonstrated in fresh (noncultured) Hodgkin's disease tumors suggesting that prolonged in vitro replication of cells derived from the tumor was necessary for its detection.…”

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Tissue culture studies in Hodgkin's disease morphologic, cytogenic, cell surface, and enzymatic properties of cultures derived from splenic tumors

Jc¹,

Zamecnik²,

Aisenberg³

et al. 1977

The Journal of Experimental Medicine

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Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.

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mentioning

confidence: 99%

Tissue culture studies in Hodgkin's disease morphologic, cytogenic, cell surface, and enzymatic properties of cultures derived from splenic tumors

Jc¹,

Zamecnik²,

Aisenberg³

et al. 1977

The Journal of Experimental Medicine

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“…Three animals had subcutaneous nodules [8][9][10] Hodgkin's disease cell lines have been maintained in vitro for 3-4 years with persistence in culture of a homogeneous population of polygonal and round cells with scattered multinuclear forms. In earlier studies from our laboratory we demonstrated an antigen on the surface and within the cytoplasm of cells from these cultures (6,7). More recently the antigen has been isolated and partially purified from supernatant medium of Hodgkin's disease cultures by polyacrylamide gel electrophoresis and Sephadex column chromatography (8).…”

mentioning

confidence: 99%

Growth of cultured cells from patients with Hodgkin's disease and transplantation into nude mice.

Zamecnik¹,

Long²

1977

Proc. Natl. Acad. Sci. U.S.A.

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Long-term monolayer cell cultures have been prepared from tumor nodules in spleens removed from 28 patients with Hodgkin's disease and from 84 spleens that did not have tumors from Hodgkin's disease patients, normal adult spleens, and human fetal spleens and thymuses. After 3 to 20 serial passages in culture, cells from nine of the Hodgkin's disease monolayers underwent morphologic change in vitro with transition from a spindle and reticular pattern of replication to polygonal and round cells that propagated in mosaic arrays. Four of such Hodgkin's disease monolayer cell lines were injected subcutaneously into 43 nude, athymic mice. In 36 animals (84%), neoplasms developed at the inoculation site that were locally destructive, capable of pulmonary metastasis, and eventually fatal to the recipients. Transplanted tumors were not observed in 18 athymic mice injected with cultures prepared from normal human adult spleen and fetal spleen and thymus, nor were tumors seen in 16 similar animals that received fresh, noncultured Hodgkin's disease tumor tissue. On microscopic examination, xenografts derived from Hodgkin's disease cultures were pleomorphic malignant neoplasms composed of large, undifferentiated cells, resembling reticulum cell sarcoma.These neoplasms did not involve the lymphoreticulr organs of mice. Chromosome studies indicated that the transplanted neoplasms were composed of human cells with an aneuploid karyotype and that monolayer cultures prepared from the heterotransplants contained a karyotype similar to that of the cultured cells prior to passage in mice. The ability of these Hodgkin's disease cell lines to produce invasive tumors with human karyotypes in nude mice is evidence of the neoplastic nature of the monolayer cells and their relationship to the malignant cell of the human disorder. (Fig. 1) appeared, interspersed among the adherent cells, particularly in the cultured nodules from Hodgkin's positive spleens. They rarely appeared in cultures from Hodgkin's negative spleens, and were never seen in cultures of normal spleens. These foci of multinucleated cells generally appeared during the end of the second week of primary culture, reached a maximal number during the third week, and then disappeared. Observation of areas containing many clusters of such multinucleated cells suggested that the giant cells were unable to divide and replicate in vitro and that they underwent degeneration and death within a week of their first appearance. (Fig. 2). Cells from four of these Hodgkin's disease cultures (FQ, RB, RY, and SP lines) were inoculated into nude mice.

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Blind Alleys in the Hodgkin's Maze

1975

The Lancet

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An Antigen in Hodgkin's Disease Tissue Cultures: Radioiodine-Labeled Antibody Studies

Abstract: An antiserum was prepared in rabbits against an antigen obtained by density gradient

Cited by 7 publications

References 16 publications

Tissue culture studies in Hodgkin's disease morphologic, cytogenic, cell surface, and enzymatic properties of cultures derived from splenic tumors

Tissue culture studies in Hodgkin's disease morphologic, cytogenic, cell surface, and enzymatic properties of cultures derived from splenic tumors

Growth of cultured cells from patients with Hodgkin's disease and transplantation into nude mice.

Blind Alleys in the Hodgkin's Maze

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