The relative expressions of VEGF-D, VEGFR1, VEGFR2, and VEGFR3 mRNA determined by qRT-PCR analyses were significantly correlated with the immunohistochemically detected levels of these proteins in primary high grade serous ovarian cancer and metastases (p = 0.004, p = 0.009, p = 0.015, and p = 0.018, respectively).
The VEGFC/VEGFR3 pathway is regarded as the principal inducer of lymphangiogenesis and it contributes to metastases; however, no data are available regarding its role during primary colorectal cancer development.
Knockdown of both FGFR4 and FLT4 significantly decreased SOX18-mediated HCC invasion and metastasis, while the stable overexpression of FGFR4 and FLT4 reversed the decrease in cell invasion and metastasis that was induced by the inhibition of SOX18.
These docetaxel-induced effects can be mitigated by anti-VEGFR3 therapy, resulting in a synergism between these treatments that reduces tumor growth and metastasis.
The expression levels of STAT3, VEGF-C, and VEGFR-3 were significantly higher in the tumor tissues of patients with axillary lymph node metastasis than in those of patients without the metastasis.
Cytoplasmic immunoexpression of VEGFR-3 in the tumour core was associated with metastasis (P=0.009), patient death (P=0.008), and histological grade (P<0.005).
Inhibition of the VEGF-C/VEGF-D/VEGFR-3 pathway by specific antibodies has been reported to efficiently inhibit experimental tumor lymphangiogenesis and metastasis in animal experiments.
Our previous studies show that activation of the VEGF-C/VEGFR-3 axis promotes cancer metastasis and is associated with clinical progression in patients with lung cancer, indicating that VEGFR-3 is a potential target for cancer therapy.
The association of VEGFR-3 expression with VEGF-C mRNA and MLC suggested that the poor prognosis and tumor metastasis associated with VEGFR-3 expression may be due, in part, to its role in promoting angiogenesis.
A close correlation was found between VEGF-C/VEGFR-3 expression and lymph node metastasis in PLC, suggesting a role in metastasis of laryngeal carcinomas.
We have assessed the therapeutic efficacy of E7080, an orally available inhibitor of multiple tyrosine kinases including VEGF receptor 2 (VEGFR-2) and VEGFR-3, in experimental multiple organ metastasis of lung cancer cell lines without EGFR mutations.
Immunohistochemistry for lymphatic vessel endothelial receptor 1 (LYVE-1), Ki-67, Twist, vascular endothelial growth factor C (VEGF-C), and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed to detect lymphatic vessel density (LVD), cell proliferation levels and the expressions of Twist, VEGF-C, and VEGFR-3 were determined from 66 primary supraglottic carcinoma tissue samples from 36 patients with lymph node metastasis (pathological N+, pN+) and 30 patients without metastasis (pathological N0, pN0).
This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits.
In contrast, VEGFTrap only suppressed primary tumor growth and metastasis to lungs by inhibiting tumor angiogenesis, whereas VEGFR3 was only effective in suppressing tumor metastasis to lymph nodes by blocking tumor lymphangiogenesis.
Many reports show that vascular endothelial growth factor receptor 3 (VEGFR3) plays an essential role in tumor metastasis and is a promising target for cancer therapy.
More importantly, the mRNA and protein expression of MMP-2, MMP-9, VEGF-C, VEGF-D and VEGFR-3 that are intimately involved in oral cancer invasion and metastasis, was simultaneously downregulated significantly as determined by quantitative real-time RT-PCR, Western blot and immunohistochemistry; and Gelatin and fibrin zymography showed that MMP-9, MMP-2 and u-PA enzymatic activities were significantly reduced in u-PAR-specific siRNA group, compared to those in control groups.
Recently, it has been revealed that lymphangiogenic growth factor VEGF-C and its receptor Flt-4 play an important role for invasion and metastasis in cancer cells.
These results indicate that quantitative analysis of lymphangiogenic marker VEGF-C and VEGFR-3 in gastroenteric specimens may be useful in predicting metastasis of gastroenteric cancer to regional lymph nodes, but the role of LYVE-1 in predicting metastasis of gastroenteric cancer requires further analysis.
VEGF-C and its VEGFR-3 played a crucial role in the regulation of tumor growth and metastasis in cervical cell lines, and COX-2 might be a regulator of VEGF-C expression.
These findings have prompted studies to investigate whether inhibitors of VEGFR-3 activation might represent novel therapeutic agents for the suppression of metastasis.