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Antibodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus
Abstract:
A clue to the molecular mechanism of neoplastic transformation was provided by the finding of a near identity in amino-acid sequence between the platelet-derived growth factor (PDGF) B-chain and a region in the transforming protein, p28sis, of simian sarcoma virus (SSV), an agent that causes sarcomas and gliomas in experimental animals. This finding infers a direct link between the molecular biology of normal mitogenesis and oncogenesis since it suggests that the transforming activity of SSV is caused by a growth factor. Although PDGF agonist activity has been isolated from conditioned medium of SSV-transformed cells, it is not clear whether infection of responsive cells by SSV leads solely to autocrine stimulation of growth by a secreted PDGF-like factor or whether other, possibly intracellular, activities of p28sis or its processed products contribute to the transformation. To distinguish between these possibilities, we have studied the effect of anti-PDGF antibodies on acute SSV-transformation, and report here that these antibodies inhibit both proliferation and SSV-induced morphological changes in human diploid fibroblasts.
Insights
Simian sarcoma virus (SSV) transformation involves a growth factor similar to platelet-derived growth factor (PDGF). Anti-PDGF antibodies were found to inhibit SSV-induced cell proliferation and morphological changes.
Area of Science:
- Oncogenesis
- Molecular Biology
- Virology
Background:
- Neoplastic transformation mechanisms are linked to growth factors.
- Simian sarcoma virus (SSV) encodes a transforming protein, p28sis, with sequence similarity to platelet-derived growth factor (PDGF) B-chain.
- This suggests SSV-induced transformation may involve autocrine growth stimulation.
Purpose of the Study:
- To investigate the role of PDGF in SSV-induced cell transformation.
- To differentiate between autocrine growth stimulation and other potential mechanisms of p28sis transforming activity.
Main Methods:
- Studied the effect of anti-PDGF antibodies on SSV-transformed human diploid fibroblasts.
- Assessed inhibition of cell proliferation and morphological changes.
Main Results:
- Anti-PDGF antibodies significantly inhibited SSV-induced proliferation.
- Anti-PDGF antibodies suppressed SSV-induced morphological alterations in fibroblasts.
- These findings support the role of PDGF in SSV transformation.
Conclusions:
- The transforming activity of SSV is significantly mediated by PDGF.
- Inhibition of PDGF signaling can counteract SSV-induced neoplastic transformation.
- This highlights the link between normal mitogenesis and oncogenesis.