Bais and colleagues argue that inhibiting PGF does not affect primary tumour growth or angiogenesis. They generated a panel of four anti-PGF monoclonal antibodies, which were selected for specificity towards mouse PGF and were shown to inhibit PGF-induced signalling through vascular endothelial growth factor receptor 1 (VEGFR1). They subcutaneously injected one of seven different mouse tumour cell lines into nude mice and found that systemic treatment with their anti-PGF antibodies mostly had no effect on tumour growth, whereas treatment with anti-VEGFA antibodies did. Although tumour growth of one allograft tumour was reduced by treatment with anti-PGF antibodies, this was not observed in a syngeneic model. Treatment with their anti-PGF antibodies also had no effect on human tumour xenografts or on the implantation of cells previously shown to be sensitive to PGF inhibition. Previous data have shown that inhibiting VEGFA increases levels of PGF, which may compensate for loss of VEGFA signalling. The authors found no evidence of increased PGF levels in the circulation or in tumour cell lysates from mice treated with an anti-VEGFA antibody. These data indicate that PGF is not upregulated in response to inhibition of VEGFA signalling, and further analyses suggest that inhibiting both VEGFA and PGF is unlikely to have an additive effect or overcome resistance to VEGFA targeted therapy. However, the authors found that anti-PGF treatment of mice bearing B16 melanomas reduced the number of metastases, confirming previous suggestions that PGF might have a role in migration and invasion as opposed to tumour angiogenesis.
How can these data be reconciled? ... Perhaps we should look at the clinical data for guidance.
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