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Pathogenesis of AIDS-associated Kaposi's sarcoma
B Ensoli1, G Barillari, R C Gallo
1Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Abstract:
Kaposi's sarcoma (KS) is a mesenchymal tumor of unclear etiopathogenesis. The epidemic form of KS occurs in up to 30% of HIV-infected individuals with lesions that have mixed cellularity, spindle cell proliferation, and neoangiogenesis. Although not completely defined, the spindle cells, thought to be the tumor cells of KS, are of mesenchymal cell origin, with features resembling endothelial and smooth muscle cells. The establishment of in vitro and in vivo model systems (AIDS-KS cell culture and the transgenic mouse model) for KS have allowed studies of the pathogenesis of KS. In particular, studies of the biologic characteristics of the AIDS-KS cells have demonstrated the presence of autocrine and paracrine growth activities. The findings of specific cytokines produced by the AIDS-KS cells may explain the histologic changes found in the KS lesion. Similarly, the development of KS-like lesions by inoculating cultured AIDS-KS cells into nude mice suggests that KS is an inducible disease. Finally, the results obtained in tat-transgenic mice and the proliferative induction of AIDS-KS cells by addition of exogenous (cell-released or recombinant) Tat protein suggest that this HIV gene product may have an important role in the development or progression of KS in HIV-infected individuals.
Insights
Kaposi's sarcoma (KS) pathogenesis is being uncovered using new models. HIV-Tat protein may play a key role in the development and progression of this mesenchymal tumor in infected individuals.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Kaposi's sarcoma (KS) is a mesenchymal tumor with complex origins, frequently affecting individuals with HIV.
- Epidemic KS lesions exhibit mixed cellularity, spindle cell proliferation, and new blood vessel formation.
- Spindle cells, the presumed tumor cells, originate from mesenchymal cells and share traits with endothelial and smooth muscle cells.
Purpose of the Study:
- To investigate the pathogenesis of Kaposi's sarcoma using established in vitro and in vivo models.
- To explore the role of specific cytokines and the HIV Tat protein in KS development and progression.
Main Methods:
- Utilized AIDS-KS cell cultures for in vitro studies.
- Employed a transgenic mouse model for in vivo investigations.
- Assessed autocrine and paracrine growth activities of AIDS-KS cells.
- Examined the effect of exogenous Tat protein on KS cell proliferation.
Main Results:
- AIDS-KS cells exhibit autocrine and paracrine growth activities, producing specific cytokines that may explain lesion histology.
- Inoculation of cultured AIDS-KS cells into nude mice induced KS-like lesions, suggesting KS is an inducible disease.
- Tat-transgenic mice developed KS-like lesions, and Tat protein induced proliferation of AIDS-KS cells.
Conclusions:
- Kaposi's sarcoma is an inducible disease, with significant implications for understanding its development in HIV-infected individuals.
- The HIV Tat protein is strongly implicated as a factor in the development or progression of Kaposi's sarcoma.
- Further research into KS pathogenesis can benefit from the established cell culture and transgenic mouse models.