Kaposi's Sarcoma Cells: Long-Term Culture with Growth Factor from Retrovirus-Infected CD4 ⁺ T Cells

Abstract

Studies of the biology and pathogenesis of Kaposi's sarcoma (KS) have been hampered by the inability to maintain long-term cultures of KS cells in vitro. In this study AIDS-KS-derived cells with characteristic spindle-like morphology were cultured with a growth factor (or factors) released by CD4+ T lymphocytes infected with human T-lymphotropic virus type I or II (HTLV-I or HTLV-II) or with human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2). Medium conditioned by HTLV-II-infected, transformed lines of T cells (HTLV-II CM) contained large amounts of this growth activity and also supported the temporary growth of normal vascular endothelial cells, but not fibroblasts. Interleukin-1 and tumor necrosis factor-alpha stimulated the growth of the KS-derived cells, but the growth was only transient and these could be distinguished from that in HTLV-II CM. Other known endothelial cell growth promoting factors, such as acidic and basic fibroblast growth factors and epidermal growth factor, did not support the long-term growth of the AIDS-KS cells. The factor released by CD4+ T cells infected with human retroviruses should prove useful in studies of the pathogenesis of KS.

Monographs on the Evaluation of Carcinogenic Risks to Humans

“…The lymphokine responsible for this growthenhancing effect has been identified as oncostatin M (Nakamura et al, 1988;Miles et al, 1992;Nair et al, 1992). This suggests that infection by other human retroviruses can lead to the production of lymphokines which promote the growth of celIs found in Kaposi's sarcomas.…”

“…ln contrast, a few other Kaposi' s sarcoma celI cultures, also of an endothelial phenotype, are angiogenic in vivo, and induce transient Kaposi's sarcoma-like vascular Iesions HUMAN IMMUNODEFICIENCY vIRUSES 153 of murine origin, when inocu1ated into nude mice (Nakamura et al, 1988;. Spindle-shaped cells grown from the peripheral blood of Kaposi' s sarcoma patients have also been reported to induce murine angiogenesis in nude mi ce (Browning et al, 1994).…”

“…A number of Iaboratories have cultured cells from Kaposi' s sarcoma that express markers characteristic for vascular or lymphatic endothelium (Delli-Bovi et al, 1986;Nakamura et al, 1988;Roth et al, 1988;Siegal et al, 1990;Corbeil et al, 1991;Herndier et aL., 1994a), but cultures expressing smooth muscle (X-actin (Albini et al, 1988;Wittek et aL., 1991) as weIl as mixed populations (Siegal et al, 1990; further references in Roth et al, 1992) have also been reported. The 1ineage identity of cuItured cells has been defined by staining for the same markers as in the in-situ studies, notably vimentin and cytokeratin (for discrimination of mesenchymal and epithelial cells respectively), the endotheIiaI markers vWF, PaI-E, OKM-5, BMA 120 (specific for bIoodvessel endotheIium), and ENA and UEA-I Iectin (reactive with bIood-vesseI and Iymphatic endotheIium), CD14, CD68 and factor XIIla (for the monocyte/macrophage lineage), SMC (X-actin (smooth muscle and myofibroblast) and others (reviewed by Roth et al, 1992;StürzI et al, 1992a;Kaaya et aL., 1995).…”

“…Members of the FGF family, including bFGF and endotheliai cell growth factor (ECFG), are known to stimuIate the growth of normal endotheliaI cells, and cultured Kaposi' s sarcoma cells with endotheliaI characteristics have been shown to Induce transient neoangiogenesis in nude mice (Nakamura et al, 1988). The FGF family of cytokines may thus play a crucial role during the development of Kaposi's sarcoma.…”

Kaposi's sarcoma

“…There are some inconsistencies. For example, an association with amyl nitrates was found in some studies (Mathur Wagh, 1985;Haverkos, 1985Haverkos, , 1987Osmond, 1985) but not in others (Goedert et al, 1986;Polk et al, 1987;Darrow et al, 1987). However there was a strong implicative association with increased numbers of partners, anoreceptive and 'rimming' practices, and previous episodes of other sexually transmitted diseases.…”