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Cultured, AIDS-related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro
Abstract:
Up to 30% of patients with acquired immunodeficiency syndrome (AIDS) suffer from Kaposi's sarcoma (AIDS-KS). The histogenesis and neoplastic nature of this tumor is still controversial. We have established cell cultures of KS biopsies from 7 patients with AIDS. All donors were seropositive for the human immunodeficiency virus I (HIV-I), cytomegalovirus (CMV) and hepatitis B virus (HBV). The tumors were histologically shown to be KS. Cell cultures derived from these tumors all expressed the endothelial cell marker BMA 120 antigen. Most of these cultures were positive for acetylated low-density lipoprotein (acLDL) uptake and alkaline phosphatase (AP) expression, and negative for factor-VIII-related antigen (FVIII-RAg). The staining pattern was heterogeneous with respect to number of endothelial cell markers expressed in each culture. We conclude from subcloning experiments that the cultured cells cease to express acLDL receptor and AP, but not the antigen detected by the monoclonal antibody (MAb) BMA 120. The cells grew well in culture up to 50 passages and showed a fibroblast-like morphology. Assays performed to investigate their degree of malignancy revealed a significantly increased passage number under reduced serum conditions as compared to normal fibroblasts but no tumor formation in nude mice. Neither HIV, HBV nor CMV sequences were found in any of the cell lines tested. We conclude that AIDS-KS is an endothelial-cell-derived neoplasm of low malignancy and that HIV, HBV and CMV are not directly involved in its genesis.
Insights
Kaposi
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Kaposi's sarcoma (KS) affects up to 30% of patients with acquired immunodeficiency syndrome (AIDS).
- The origin and neoplastic nature of AIDS-related Kaposi's sarcoma (AIDS-KS) remain debated.
- Human immunodeficiency virus I (HIV-I), cytomegalovirus (CMV), and hepatitis B virus (HBV) were present in donors.
Purpose of the Study:
- To establish and characterize cell cultures from AIDS-KS biopsies.
- To investigate the cellular origin and malignant potential of AIDS-KS.
- To determine the direct involvement of HIV, HBV, and CMV in AIDS-KS genesis.
Main Methods:
- Established cell cultures from KS biopsies of 7 HIV-positive patients.
- Analyzed endothelial cell markers (BMA 120, acLDL uptake, AP, FVIII-RAg).
- Performed subcloning, long-term culture (up to 50 passages), and nude mouse xenografts.
- Tested for viral sequences (HIV, HBV, CMV).
Main Results:
- Cultured cells expressed endothelial markers (BMA 120, acLDL, AP) but lost some markers upon subcloning.
- Cells exhibited fibroblast-like morphology, grew well in culture, and showed increased passage under reduced serum.
- No tumor formation was observed in nude mice, and no viral sequences were detected in cell lines.
Conclusions:
- AIDS-KS is an endothelial-cell-derived neoplasm with low malignancy.
- HIV, HBV, and CMV are not directly implicated in the oncogenesis of AIDS-KS.
- Cultured AIDS-KS cells provide a model for studying the tumor's biology.