Compared to primary high grade serous ovarian tumors, the related omental metastases showed higher expressions of VEGF-A (p = 0.022), VEGF-D (p = 0.010), and VEGFR1 (p = 0.046).
In addition, patients with higher VEGFR1 expression levels were more likely to develop distant metastases than those with lower VEGFR1 expression levels (P = 0.049).
Preclinical studies have suggested that VEGFR1-positive cells potentially foster the development of metastases by establishing a "premetastatic niche."
Moreover, we found that the soluble Flt-1 from SWT neutralized the increased placental growth factor (PLGF) secreted by the metastatic cancer cells after primary cancer resection and subsequently inhibited the cancer neovascularization to suppress the metastatic cancer growth.
Importantly, FLT1 inhibition reduces tumor metastatic efficiency even after initial seeding, suggesting that these pathways represent therapeutic targets in metastatic disease.
These findings demonstrate that the VEGF-VEGFR1 signaling pathway is crucial for tumor metastasis and the blockade of VEGF-VEGFR1-induced metastasis may provide a novel approach for the prevention and treatment of tumor metastasis.
Flow cytometry analysis disclosed that vascular endothelial growth factor receptor-1 expressing cells in the peripheral blood were more abundant in cancer cases with metastases than in cases without metastases.