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The pattern of susceptibility of malignant cells to the cytostatic drug suramin is not fully clarified. Therefore, in the present paper we have assessed the effects of suramin on the growth of eight cell lines derived from human malignant fibrous histiocytomas, by measuring DNA synthesis. The effect of suramin (10-200 microg/ml) on cells either unstimulated, or stimulated with platelet-derived growth factor (PDGF)-AA (10 ng/ml), PDGF-BB (10 ng/ml) or 10% fetal calf serum was studied. Four out of five cell lines unable to thrive without external growth factors showed growth inhibition by suramin. The two cell lines able to grow under serum-free conditions were unaffected by high-dose suramin. The exposure to suramin, at 200 microg/ml, abolished the growth stimulation caused by PDGF-AA and -BB. In contrast, a low dose of suramin (50 microg/ml), with or without PDGF, caused growth-stimulating effects in some cell lines. Our results indicate that high doses of suramin inhibit growth of malignant fibrous histiocytomas in vitro and that suramin exerts its growth-inhibitory effects on cells dependent on external growth factors. Low-dose treatment with suramin, however, may instead promote growth in both serum-dependent and -independent tumor cell lines.

Platelet-derived growth factor (PDGF) has been proposed to play an important role in the growth of tumors. In order to study the effects of PDGF-AB on tumor growth in vivo, sarcoma-bearing mice were treated with PDGF-AB. The tumors, a malignant fibrous histiocytoma and an osteosarcoma, had functional PDGF receptors in vitro, as demonstrated by stimulation of PDGF-AB using a [3H]thymidine incorporation assay. Immunohistochemistry also revealed that both sarcoma xenografts expressed PDGF receptors. The tumor-bearing mice were given human PDGF-AB for 14 days, either continuously by an intraperitoneally placed mini-osmotic pump, or by daily injections. No effects on tumor growth in vivo were observed, as measured by tumor volume, autoradiography or cell cycle distribution. The histological appearance and ploidy of the tumors remained unaltered. The results indicate that, although the tumor cells are stimulated by PDGF-AB in vitro, the in vivo milieu or tumor growth pattern may render the tumors less susceptible to exogenously administered PDGF-AB in vivo.

Eight human malignant fibrous histiocytomas were examined in vitro, in order to relate their growth properties to mRNA expression for platelet-derived growth factor (PDGF), PDGF receptor (PDGF-R), transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGF-R). Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that all cell lines expressed mRNA for PDGF-R alpha and/or PDGF-R beta; six cell lines expressed mRNA for the PDGF-A chain, with one cell line coexpressing PDGF-B chain mRNA; seven cell lines expressed mRNA for TGF-alpha whereas six cell lines expressed EGF-R mRNA. Conditioned medium from three cell lines contained PDGF; none of the cell lines released TGF-alpha. Two cell lines grew without serum requirements; whereas both expressed mRNA for PDGF, PDGF-R, TGF-alpha and EGF-R, other cell lines, unable to grow without serum, showed the same combination of growth factor/growth factor receptor expression. The two cell lines able to grow without serum were also shown to be stimulated by the addition of PDGF-BB. These findings show that simultaneous expression of mRNA for a growth factor and its receptor does not necessarily imply an autocrine or paracrine loop. However, two of our cell lines fulfil the requirements of possible PDGF-related autocrine and paracrine regulation.

The kinetics of exogenously given 125I-platelet-derived growth factor-AB (PDGF-AB) was studied in mice. 125I-PDGF-AB was injected either intraperitoneally, intramuscularly or subcutaneously and the resulting concentrations of 125I-radioactivity monitored in the blood at different times. The serum levels of 125I-radioactivity rose to a maximum 2-4 hours after injection, before decreasing. Precipitation of serum with trichloroacetic acid demonstrated that 50 per cent or more of the 125I remained in macromolecular form. Further, gel chromatography studies showed that the molecular size of the labelled material in serum, three hours after injection, was the same as that of the original 125I-PDGF-AB. In addition, a low-molecular weight fraction was observed, indicating the presence of degradation products. The largest proportion of degraded material was obtained after subcutaneous administration. The absence of partially degraded 125I-labelled fragments, e.g. 125I oligopeptides, indicates complete rather than limited degradation and suggests that the 125I-PDGF-AB had been processed by cellular uptake. It is concluded that extra-vascularly given PDGF-AB in mice is taken up into the blood in intact macromolecular form. This finding suggests that it is possible to administer PDGF extravascularly to obtain a prolonged increase in the concentration of intact PDGF in the blood.