Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma

Yanto Lunardi-Iskandar, Parkash Gill, Victor H. Lam, Robert A. Zeman, Frank Michaels, Dean L. Mann, Marvin S. Reitz, Mark Kaplan, Zwi N. Berneman, Darryl Carter, Joseph L. Bryant, Robert C. Gallo

Research output: Contribution to journalArticle

Abstract

Background: Acquired immunodeficiency syndrome (AIDS) is associated with the occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However, no evidence exists yet that human immunodeficiency virus type 1, the causative agent of AIDS, is directly responsible for cell transformation. It is also not clear whether KS lesions, which are of complex cellularity, contain tumor cells derived from a true monoclonal malignancy (originating from a single malignant cell) or whether the lesions are just polyclonally hyperplastic in nature (containing increased numbers of normal cells). In fact, the presence of malignant KS cells has never been unequivocally shown in AIDS-associated KS, and previously isolated KS cell cultures were not immortal or malignant. Purpose: Our purpose was to (a) utilize technology that could facilitate isolation and enrichment of tumor cells from AIDS-associated KS lesions, (b) establish and characterize an immortalized KS cell line, and (c) test the malignant potential of such a cell line in animal models. Methods: Mononuclear cells were isolated from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes, B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a cytotoxicity method, using monoclonal antibodies specific for cell surface markers and baby rabbit complement. KS cells were cultured in the absence of exogenous growth factors in an effort to select for transformed cells capable of self-sustained growth. The karyotype abnormalities were detected by G-banded marker studies, and phenotypic markers were determined by indirect immunofluorescence and immunocytochemical methods. Beige nude XID and severe combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic, and metastatic potentials of cells. Results: An immortalized cell line, named KS Y-1, was isolated. Its phenotype is similar to that of endothelial cells with positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found in primary fresh KS tissue and in vitro passages of KS Y-1 cells. These cells promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice. Tumors produced at the site of injection, as well as metastases in the lung, spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid karyotype. KS Y-1 cells show high plating efficiency. Conclusion: The KS Y-1 cell line could be the first evidence of AIDS-associated KS cells that may develop clones with an indisputable malignant cell phenotype. Implications: KS Y-1 cells in the in vivo mouse model can be used to study the effects of therapeutic compounds in advanced KS.

Original languageEnglish (US)
Pages (from-to)974-981
Number of pages8
JournalJournal of the National Cancer Institute
Volume87
Issue number13
StatePublished - Jul 5 1995

Fingerprint

Kaposi's Sarcoma
Isolation
Acquired Immunodeficiency Syndrome
Cells
Cell Line
Line
Cell
Tumors
Monoclonal antibodies
T-cells
Lymphocytes
Macrophages
Tumor
Endothelial cells
Fibroblasts
Cytotoxicity
Cell line
Viruses
Cell culture
Plating

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Lunardi-Iskandar, Y., Gill, P., Lam, V. H., Zeman, R. A., Michaels, F., Mann, D. L., ... Gallo, R. C. (1995). Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma. Journal of the National Cancer Institute, 87(13), 974-981.

Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma. / Lunardi-Iskandar, Yanto; Gill, Parkash; Lam, Victor H.; Zeman, Robert A.; Michaels, Frank; Mann, Dean L.; Reitz, Marvin S.; Kaplan, Mark; Berneman, Zwi N.; Carter, Darryl; Bryant, Joseph L.; Gallo, Robert C.

In: Journal of the National Cancer Institute, Vol. 87, No. 13, 05.07.1995, p. 974-981.

Research output: Contribution to journalArticle

Lunardi-Iskandar, Y, Gill, P, Lam, VH, Zeman, RA, Michaels, F, Mann, DL, Reitz, MS, Kaplan, M, Berneman, ZN, Carter, D, Bryant, JL & Gallo, RC 1995, 'Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma', Journal of the National Cancer Institute, vol. 87, no. 13, pp. 974-981.
Lunardi-Iskandar Y, Gill P, Lam VH, Zeman RA, Michaels F, Mann DL et al. Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma. Journal of the National Cancer Institute. 1995 Jul 5;87(13):974-981.
Lunardi-Iskandar, Yanto ; Gill, Parkash ; Lam, Victor H. ; Zeman, Robert A. ; Michaels, Frank ; Mann, Dean L. ; Reitz, Marvin S. ; Kaplan, Mark ; Berneman, Zwi N. ; Carter, Darryl ; Bryant, Joseph L. ; Gallo, Robert C. / Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma. In: Journal of the National Cancer Institute. 1995 ; Vol. 87, No. 13. pp. 974-981.
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abstract = "Background: Acquired immunodeficiency syndrome (AIDS) is associated with the occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However, no evidence exists yet that human immunodeficiency virus type 1, the causative agent of AIDS, is directly responsible for cell transformation. It is also not clear whether KS lesions, which are of complex cellularity, contain tumor cells derived from a true monoclonal malignancy (originating from a single malignant cell) or whether the lesions are just polyclonally hyperplastic in nature (containing increased numbers of normal cells). In fact, the presence of malignant KS cells has never been unequivocally shown in AIDS-associated KS, and previously isolated KS cell cultures were not immortal or malignant. Purpose: Our purpose was to (a) utilize technology that could facilitate isolation and enrichment of tumor cells from AIDS-associated KS lesions, (b) establish and characterize an immortalized KS cell line, and (c) test the malignant potential of such a cell line in animal models. Methods: Mononuclear cells were isolated from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes, B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a cytotoxicity method, using monoclonal antibodies specific for cell surface markers and baby rabbit complement. KS cells were cultured in the absence of exogenous growth factors in an effort to select for transformed cells capable of self-sustained growth. The karyotype abnormalities were detected by G-banded marker studies, and phenotypic markers were determined by indirect immunofluorescence and immunocytochemical methods. Beige nude XID and severe combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic, and metastatic potentials of cells. Results: An immortalized cell line, named KS Y-1, was isolated. Its phenotype is similar to that of endothelial cells with positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found in primary fresh KS tissue and in vitro passages of KS Y-1 cells. These cells promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice. Tumors produced at the site of injection, as well as metastases in the lung, spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid karyotype. KS Y-1 cells show high plating efficiency. Conclusion: The KS Y-1 cell line could be the first evidence of AIDS-associated KS cells that may develop clones with an indisputable malignant cell phenotype. Implications: KS Y-1 cells in the in vivo mouse model can be used to study the effects of therapeutic compounds in advanced KS.",
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AU - Zeman, Robert A.

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