RESUMEN
BACKGROUND: Kaposi's sarcoma (KS) is a tumor whose ontogenic origin remains a matter of contention. KS tissues are characterized by predominant expression of endothelial markers, while KS-derived cell cultures are usually characterized by expression of mesenchymal non-endothelial cell markers. AIMS: In order to clarify the ontogenic origin of KS cells, we investigated the expression of the fibroblast/macrophage marker 1B10 in KS tissues (AIDS-associated KS, n = 9; classic KS, n = 6; iatrogenic KS, n = 6) and in KS-derived cell cultures. RESULTS: 1B10 was expressed by loosely distributed spindle-shaped cells in early 'patch-stage' KS and by a variable proportion of spindle cells in late 'plaque- and nodular-stage' KS. Using immunohistochemistry and immunoblot analysis, we found that, in vitro, reactivity for 1B10 was uniformly evidenced in fibroblasts and in KS-derived spindle cell cultures, irrespective of their histological or epidemiological setting. By contrast, vascular smooth muscle cells and endothelial cells were negative for 1B10. CONCLUSIONS: These results suggest that the KS spindle cells isolated in vitro may represent a particular subpopulation of the KS spindle cell compartment.
Asunto(s)
Antígenos de Superficie/biosíntesis , Biomarcadores de Tumor/análisis , Sarcoma de Kaposi/metabolismo , Neoplasias Cutáneas/metabolismo , Antígenos de Superficie/análisis , Biopsia , Fibroblastos/metabolismo , Inmunohistoquímica , Macrófagos/metabolismo , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Células Tumorales CultivadasRESUMEN
Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, we have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS). We have also shown that the iron chelator desferrioxamine (DFO) has a potent anti-KS activity in vitro, suggesting that it may represent a potential therapeutic approach for the treatment of KS. The present study was designed to investigate the effect of DFO on the growth of human KS xenografts in immunodeficient mice. Unexpectedly, we found that mice treated with DFO (400 mg/kg, 3 times weekly) (n = 30) exhibited a marked enhancement of tumor growth compared with control mice (n = 33) (230 +/- 134 mm(2) versus 143 +/- 70 mm p < 0.01). No enhancement of tumor growth was seen in mice treated with iron-saturated DFO. At least 2 findings suggest that this paradoxic pro-KS activity occurred independently of mice iron stores. First, treatment with DFO had only a marginal effect on ferritin and hematocrit levels. Second, induction of effective iron depletion by an iron-poor diet (6.7 mg iron/kg diet) (n = 23) did not have a deleterious effect on the growth of the KS xenografts. The lesions obtained from the DFO-treated animals exhibited a significantly decreased apoptotic index (p < 0.05), indicating that some antiapoptotic mechanism induced by DFO may be operating in vivo to favour tumor growth. In conclusion, our data show that DFO has a stimulatory effect on KS growth in immunodeficient mice, suggesting that this drug is not indicated in patients with KS.