Spindle cell ploidy and proliferation in endemic and epidemic African Kaposi's sarcoma

Kaaya, Ephata; Parravicini, Carlo; Sundelin, Birgitta; Mgaya, Edward; Kitinya, James; Lema, Leonard; Luande, J.; Biberfeld, Peter

doi:10.1016/0959-8049(92)90030-6

Cited by 32 publications

(17 citation statements)

References 20 publications

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“…More than 90% of KS cells were judged to be viable by the criteria of Trypan-blue exclusion and cell morphology. Iron exerted stimulatory effects on the 4 KS cell cultures studied, which is in agreement with studies showing that the spindle-cell component of the different epidemiological settings of KS has common biological and/or pathological characteristics (Kaaya et al, 1992;Benelli et al, 1994). By contrast, there was little or no effect on the growth of the immortalized AIDS-KS cell line KS-Y1 (Fig.…”

Section: Iron-induced Growth Stimulationsupporting

confidence: 78%

Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?

et al. 1998

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The role of iron in the pathogenesis of several tumours is being increasingly investigated. In particular, its involvement in the pathogenesis of Kaposi's sarcoma (KS) is suggested by the distribution of the endemic form of KS corresponding to continental rifts and associated iron‐oxide‐rich volcanic clays. We investigated in vitro to what extent iron supplementation or withdrawal could affect the growth of KS‐derived cells, by analysing the effects of adding iron salts (iron chloride and ferric nitrilotriacetate) and/or reducing iron by iron chelators (desferrioxamine) on KS‐derived cell cultures. The addition of iron salts strongly stimulated the growth of KS cells, as reflected by increase in thymidine incorporation and cell number. Conversely, desferrioxamine and deferiprone inhibited cell growth. The inhibitory effect of iron chelation was more pronounced on rapidly dividing basic fibroblast‐growth‐factor‐stimulated cells. These results may point to a novel therapeutic approach to KS. Int. J. Cancer 78:720–726, 1998. © 1998 Wiley‐Liss, Inc.

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Section: Iron-induced Growth Stimulationsupporting

confidence: 78%

Iron as a potential co-factor in the pathogenesis of Kaposi's sarcoma?

et al. 1998

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“…Therefore, from an evolutionary perspective, it is conceivable that even low-level lytic replication observed in the early-stage KS lesions may exert significant cumulative selective pressure to drive the emergence of clones with elevated K13 expression and dysregulated expression of viral and cellular genes. Another unique property of KS—their relatively low proliferative rate [64]—may also magnify the impact of even low-level lytic replication on tumor composition over time. Finally, although the level of lytic replication in early-stage KS is low, these lesions do demonstrate large numbers of apoptotic cell, and there is a dramatic decline in the number of apoptotic cells with lesion progression with an associated increase in K13 expression [29].…”

Section: Discussionmentioning

confidence: 99%

K13 Blocks KSHV Lytic Replication and Deregulates vIL6 and hIL6 Expression: A Model of Lytic Replication Induced Clonal Selection in Viral Oncogenesis

et al. 2007

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BackgroundAccumulating evidence suggests that dysregulated expression of lytic genes plays an important role in KSHV (Kaposi's sarcoma associated herpesvirus) tumorigenesis. However, the molecular events leading to the dysregulation of KSHV lytic gene expression program are incompletely understood.Methodology/Principal FindingsWe have studied the effect of KSHV-encoded latent protein vFLIP K13, a potent activator of the NF-κB pathway, on lytic reactivation of the virus. We demonstrate that K13 antagonizes RTA, the KSHV lytic-regulator, and effectively blocks the expression of lytic proteins, production of infectious virions and death of the infected cells. Induction of lytic replication selects for clones with increased K13 expression and NF-κB activity, while siRNA-mediated silencing of K13 induces the expression of lytic genes. However, the suppressive effect of K13 on RTA-induced lytic genes is not uniform and it fails to block RTA-induced viral IL6 secretion and cooperates with RTA to enhance cellular IL-6 production, thereby dysregulating the lytic gene expression program.Conclusions/SignificanceOur results support a model in which ongoing KSHV lytic replication selects for clones with progressively higher levels of K13 expression and NF-κB activity, which in turn drive KSHV tumorigenesis by not only directly stimulating cellular survival and proliferation, but also indirectly by dysregulating the viral lytic gene program and allowing non-lytic production of growth-promoting viral and cellular genes. Lytic Replication-Induced Clonal Selection (LyRICS) may represent a general mechanism in viral oncogenesis.

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“…1). However, when PAF was measured after 48 h of growth without FCS in (8)(9)(10)(11)(12). We thus studied the effect of PAF on the migration and proliferation of KS cells, EC, VSMC, and macrophage murine cell line J774.…”

Section: Resultsmentioning

confidence: 99%

“…The ontogenetic origin of KS has not been unequivocally defined (8)(9)(10)(11)(12). Spindle cells represent the core of the lesion and consist of at least two populations, one expressing fibro-endothelial markers and the other a phenotype typical of monocytoid cells (11). Furthermore, they also express smooth muscle a-actin (58,59).…”

Section: Discussionmentioning

confidence: 99%

“…The early phase of disease is characterized by an infiltrate of leukocytes and a prominent angiogenesis, which is crucial to the growth and progression of KS (8)(9)(10)(11)(12). The current hypothesis to explain the behavior of KS is an imbalance in the network of soluble mediators caused by HIV-1, other viruses, immunosuppressive treatment, or genetic factors (13)(14)(15)(16)(17)(18).…”

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confidence: 99%

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