We show that α<sub>2</sub>-antiplasmin restricts activation of VEGF-D, enlargement of intra-tumoural lymphatics and occurrence of lymph node metastasis.
Vascular endothelial growth factor D (VEGF-D) is a key lymphangiogenic factor that is associated with lymphangiogenesis and lymph node metastasis in GBC.
However, little is known regarding the functional relationship between Sema4D and VEGF-C/VEGF-D and in the mediation of lymphangiogenesis and lymph node metastasis and clinical outcome.
To explore the necessity of processing for the effects of VEGF-D in cancer, we use a mutant full-length form that cannot be processed, and show that, in contrast to full-length VEGF-D that is processed, this mutant does not promote tumor growth and lymph node metastasis in a mouse tumor model.
The group with high expression of VEGF-C and VEGF-D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression.
It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated.
VEGF-C and VEGF-D expressions were associated with VEGFR-3 expression and were significantly correlated with both peritumoral lymphangiogenesis and lymph node metastasis.
Because a comparable transgenic expression of vascular endothelial growth factor-C (VEGF-C) in Rip1Tag2 has been shown previously to provoke lymphangiogenesis and lymph node metastasis in the absence of any distant metastasis, leukocyte infiltration, or angiogenesis-suppressing effects, these results reveal further functional differences between VEGF-D and VEGF-C.
The expression of VEGF-D protein and mRNA levels in patients without lymph node metastasis were significantly higher than those with metastasis (p=0.013, p=0.0494, respectively).
In conclusion, our findings indicate that VEGF-D expression and increased lymph vessel density may have an important role for lymph node metastasis in papillary thyroid carcinoma.
Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1alpha) and the HIF-1alpha target gene DEC1, but not lymph node metastasis in primary human breast carcinomas.
Our results suggest that a decrease in VEGF-D mRNA or an increase in the VEGF-C/VEGF-D ratio may have an association with tumorigenesis and/or lymph node metastasis in breast cancer.
However, two-way scatterplot analysis revealed that tumors with lymph node metastasis were associated with a pattern of low VEGF-D and high VEGF-A, VEGF-B, or VEGF-C, such that the ratios of VEGF-D:VEGF-A, VEGF-D:VEGF-B, or VEGF-D:VEGF-C were significantly lower in the node-positive group.