Search

Aim: To study the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C and to determine whether the presence of VEGF-A and VEGF-C was associated with the clinicopathologic characteristics of pancreatic cancer., Methods: VEGF-A and VEGF-C mRNA transcripts were examined by Northern blot in 6 human pancreatic cancer cell lines and 8 normal pancreatic tissues and 8 pancreatic carcinoma specimens. The expression of VEGF-A and VEGF-C proteins was examined by Western blot in the tested cell lines and by immunohistochemical stain in 50 pancreatic carcinoma samples., Results: VEGF-A and VEGF-C mRNA transcripts were present in all the 6 human pancreatic cancer cell lines. Immunoblotting revealed the presence of VEGF-A and VEGF-C proteins in all the cell lines. Northern blot analysis of total RNA revealed 3.0-fold and 3.6-fold increase in VEGF-A and VEGF-C mRNA transcript in the cancer samples, respectively. Immunohistochemical analysis confirmed the expression of VEGF-A and VEGF-C in cancer cells within the tumor mass. Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A and VEGF-C immunoreactivity in 50% and 80% of the cancer tissue samples, respectively. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread (c2 = 6.690, P = 0.035<0.05) but was not associated with decreased patient survival. However, the presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis (c2 = 5.710, P = 0.017 < 0.05), but was not associated with decreased patient survival. There was no correlation between the expression of VEGF-A and VEGF-C in the same cancer cells., Conclusion: VEGF-A and VEGF-C are commonly overexpressed in human pancreatic cancer and may contribute to tumor growth and lymph node metastasis. There is no relationship between the expression of VEGF-A and VEGF-C in pancreatic cancer.

Background: Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells--stromal cell interaction, which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-1alpha(IL-1alpha), and interleukin-6 (IL-6)., Methods: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer, we used the reverse transcription-polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1alpha(10 microg/L) or IL-6 (100 microg/L)., Results: Northern blot analysis revealed the presence of the 4.1 kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-1alpha, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but no effect was found in the COLO-357 cell line., Conclusion: These findings suggested that the expression of VEGF-A, C and their regulation by IL-1alpha, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in cancer growth. In this study, we characterized VEGF-C expression in cultured human pancreatic cancer cell lines and determined whether the presence of VEGF-C in human pancreatic cancers is associated with clinicopathologic characteristics. VEGF-C mRNA transcripts were present in all five tested cell lines (Capan-1, MIA-PaCa-2, PANC-1, COLO-357, and T3M4). Immunoblotting with a highly specific anti-VEGF-C antibody revealed the presence of VEGF-C protein in all the cell lines. Northern blot analysis of total RNA revealed an approximately 2.2-fold increase in VEGF-C mRNA transcript in the cancer samples compared with the normal pancreas. Immunohistochemical analysis confirmed the expression of VEGF-C and its receptor flt-4 in the cancer cells within the tumor mass. Immunohistochemical analysis of 51 pancreatic cancer tissues revealed the presence of strong VEGF-C immunoreactivity in the cancer cells in 80.4% of the cancer tissues. The presence of VEGF-C in these cells was associated with increased lymphatic vessels invasion and lymph node metastasis, but not with decreased patient survival. These findings indicate that VEGF-C and its receptor are commonly overexpressed in human pancreatic cancers and that this factor may contribute to the lymphangiogenic process and metastasis in this disorder.