Skip to main content
Erschienen in: Medical Oncology 4/2010

01.12.2010 | Original Paper

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters

verfasst von: Qi-Lian Liang, Bi-Rong Wang, Guo-Qiang Chen, Guo-Hong Li, Yan-Yun Xu

Erschienen in: Medical Oncology | Ausgabe 4/2010

Einloggen, um Zugang zu erhalten

Abstract

Vasiformation is essential for the growth and metastasis of tumor. Vascular endothelial growth factor (VEGF) and connexin43 (Cx43) are important regulatory factors of vasiformation. This study aimed to find out the expression features of VEGF and Cx43 and their significance in pancreatic cancer. The expression levels of VEGF and Cx43 protein in the samples, which came from 100 patients of human pancreatic cancer tissues and adjacent normal pancreatic tissues, were examined by using immunohistochemical streptavidin–peroxidase (S–P) method, Western-blotting, and RT–PCR analyses. Compared with adjacent normal pancreatic tissues, RT–PCR showed that the expression of VEGF mRNA was significantly higher in pancreatic cancer tissues (0.788 ± 0.290, P < 0.01) and Cx43 mRNA was significantly lower in pancreatic cancer tissues (0.403 ± 0.204, P < 0.01). The expression of VEGF protein was higher in pancreatic cancer tissue (0.745 ± 0.254, P < 0.01) by Western-blot, and Cx43 protein was obviously lower in pancreatic cancer tissues (0.373 ± 0.164, P < 0.01). The immunohistochemical S–P method showed as follows: the positive expression rate of VEGF and Cx43 protein was 77 and 48% in pancreatic cancer tissues and 15 and 100% in adjacent normal pancreatic tissues; expressions of VEGF were related to tumor size, TNM stage, and lymph node metastasis (P < 0.05); there was a close relation between the expression of Cx43 and histological grades, TNM stage, and lymph node metastasis (P < 0.05). This present study suggests that VEGF is overexpressed and the expression of Cx43 is lower in pancreatic cancer. The expression of VEGF and Cx43 is significantly correlated with TNM stage and lymph node metastasis. Furthermore, VEGF and Cx43 may play an important role in the occurrence, development, and metastasis of pancreatic cancer. To examine VEGF and Cx43 may be of value in judging the malignancy degree and the prognosis of pancreatic cancer.
Literatur
1.
Zurück zum Zitat Simon KW, Roberts PC, Vespremi MJ, Manchen S, Schmelz EM. Regulation of beta-catenin and connexin-43 expression: targets for sphingolipids in colon cancer prevention. Mol Nutr Food Res. 2009;53(3):332–40. PMID: 17627324.PubMedCrossRef Simon KW, Roberts PC, Vespremi MJ, Manchen S, Schmelz EM. Regulation of beta-catenin and connexin-43 expression: targets for sphingolipids in colon cancer prevention. Mol Nutr Food Res. 2009;53(3):332–40. PMID: 17627324.PubMedCrossRef
2.
Zurück zum Zitat Upham BL, Blaha L, Babica P, Park JS, Sovadinova L, Pudrith C, et al. Tumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine-specific phospholipase C. Cancer Sci. 2008;99:696–705. PMID: 18377422.PubMedCrossRef Upham BL, Blaha L, Babica P, Park JS, Sovadinova L, Pudrith C, et al. Tumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine-specific phospholipase C. Cancer Sci. 2008;99:696–705. PMID: 18377422.PubMedCrossRef
3.
Zurück zum Zitat Sato H, Hagiwara H, Ohde Y, Senba H, Virgona N, Yano T. Regulation of renal cell carcinoma cell proliferation, invasion and metastasis by connexin 32 gene. J Membr Biol. 2007;216:17–21. PMID: 17565422.PubMedCrossRef Sato H, Hagiwara H, Ohde Y, Senba H, Virgona N, Yano T. Regulation of renal cell carcinoma cell proliferation, invasion and metastasis by connexin 32 gene. J Membr Biol. 2007;216:17–21. PMID: 17565422.PubMedCrossRef
4.
Zurück zum Zitat Udaka N, Miyagi Y, Ito T. Connexin expression in mouse lung tumor. Cancer Lett. 2007;246:224–9. PMID: 16580773.PubMedCrossRef Udaka N, Miyagi Y, Ito T. Connexin expression in mouse lung tumor. Cancer Lett. 2007;246:224–9. PMID: 16580773.PubMedCrossRef
5.
Zurück zum Zitat Duncan TJ, Al-Attar A, Rolland P, Scott IV, Deen S, Liu DT, et al. Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies? Clin Cancer Res. 2008;14:3030–5. PMID:18483368.PubMedCrossRef Duncan TJ, Al-Attar A, Rolland P, Scott IV, Deen S, Liu DT, et al. Vascular endothelial growth factor expression in ovarian cancer: a model for targeted use of novel therapies? Clin Cancer Res. 2008;14:3030–5. PMID:18483368.PubMedCrossRef
6.
Zurück zum Zitat Wong ET, Brem S. Antiangiogenesis treatment for glioblastoma multiforme: challenges and opportunities. J Natl Compr Canc Netw. 2008;6:515–22. PMID: 18492463.PubMed Wong ET, Brem S. Antiangiogenesis treatment for glioblastoma multiforme: challenges and opportunities. J Natl Compr Canc Netw. 2008;6:515–22. PMID: 18492463.PubMed
7.
Zurück zum Zitat Tsirlis TD, Papastratis G, Masselou K, Tsigris C, Papachristodoulou A, Kostakis A, et al. Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance? World J Gastroenterol. 2008;14:2691–701. PMID:18461654.PubMedCrossRef Tsirlis TD, Papastratis G, Masselou K, Tsigris C, Papachristodoulou A, Kostakis A, et al. Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance? World J Gastroenterol. 2008;14:2691–701. PMID:18461654.PubMedCrossRef
8.
Zurück zum Zitat Wu J, Zhou HF, Wang CH, Zhang B, Liu D, Wang W, et al. Decreased expression of Cx32 and Cx43 and their function of gap junction intercellular communication in gastric cancer. Zhonghua Zhong Liu Za Zhi. 2007;29:742–7. (in Chinese) PMID: 18396685.PubMed Wu J, Zhou HF, Wang CH, Zhang B, Liu D, Wang W, et al. Decreased expression of Cx32 and Cx43 and their function of gap junction intercellular communication in gastric cancer. Zhonghua Zhong Liu Za Zhi. 2007;29:742–7. (in Chinese) PMID: 18396685.PubMed
9.
Zurück zum Zitat Avanzo JL, Mennecier G, Mesnil M, Hernandez-Blazquez FJ, Fukumasu H, da Silva TC, et al. Deletion of a single allele of Cx43 is associated with a reduction in the gap junctional intercellular communication and increased cell proliferation of mouse lung pneumocytes type II. Cell Prolif. 2007;40(3):411–21. PMID:17531084.PubMedCrossRef Avanzo JL, Mennecier G, Mesnil M, Hernandez-Blazquez FJ, Fukumasu H, da Silva TC, et al. Deletion of a single allele of Cx43 is associated with a reduction in the gap junctional intercellular communication and increased cell proliferation of mouse lung pneumocytes type II. Cell Prolif. 2007;40(3):411–21. PMID:17531084.PubMedCrossRef
10.
Zurück zum Zitat Breen E, Tang K, Olfert M, Knapp A, Wagner P. Skeletal muscle capillarity during hypoxia: VEGF and its activation. High Alt Med Biol. 2008;9:158–66. PMID: 18578647.PubMedCrossRef Breen E, Tang K, Olfert M, Knapp A, Wagner P. Skeletal muscle capillarity during hypoxia: VEGF and its activation. High Alt Med Biol. 2008;9:158–66. PMID: 18578647.PubMedCrossRef
11.
Zurück zum Zitat Oh SY, Kwon HC, Kim SH, Jang JS, Kim MC, Kim KH, et al. Clinicopathologic significance of HIF-1alpha, p53, VEGF expression, preoperative serum VEGF level in gastric cancer. BMC Cancer. 2008;8:123. PMID: 18452596.PubMedCrossRef Oh SY, Kwon HC, Kim SH, Jang JS, Kim MC, Kim KH, et al. Clinicopathologic significance of HIF-1alpha, p53, VEGF expression, preoperative serum VEGF level in gastric cancer. BMC Cancer. 2008;8:123. PMID: 18452596.PubMedCrossRef
12.
Zurück zum Zitat Noma K, Smalley KS, Lioni M, Naomoto Y, Tanaka N, El-Deiry W, et al. The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology. 2008;134:1981–93. PMID: 18439605.PubMedCrossRef Noma K, Smalley KS, Lioni M, Naomoto Y, Tanaka N, El-Deiry W, et al. The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology. 2008;134:1981–93. PMID: 18439605.PubMedCrossRef
13.
Zurück zum Zitat Mimura K, Kono K, Takahashi A, Kawaguchi Y, Mizukami Y, Fujii H. Vascular endothelial growth factor partially inhibits the trastuzumab-mediated antibody-dependent cellular cytotoxicity of human monocytes. Oncology. 2007;72:172–80. PMID: 18097168.PubMedCrossRef Mimura K, Kono K, Takahashi A, Kawaguchi Y, Mizukami Y, Fujii H. Vascular endothelial growth factor partially inhibits the trastuzumab-mediated antibody-dependent cellular cytotoxicity of human monocytes. Oncology. 2007;72:172–80. PMID: 18097168.PubMedCrossRef
14.
Zurück zum Zitat De Maio A, Vega VL, Contreras JE. Gap junctions, homeostasis, and injury. Cell Physiol. 2002;191:269–82. PMID: 12012322.CrossRef De Maio A, Vega VL, Contreras JE. Gap junctions, homeostasis, and injury. Cell Physiol. 2002;191:269–82. PMID: 12012322.CrossRef
15.
Zurück zum Zitat Yano T, Fujimoto E, Hagiwara H, Sato H, Yamasaki H, Negishi E, et al. Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma. Biol Pharm Bull. 2006;29:1991–4. PMID: 17015938.PubMedCrossRef Yano T, Fujimoto E, Hagiwara H, Sato H, Yamasaki H, Negishi E, et al. Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma. Biol Pharm Bull. 2006;29:1991–4. PMID: 17015938.PubMedCrossRef
16.
Zurück zum Zitat Zhang XF, Ren ZY, Fang FD, Zuo J, Su CB, Wang RZ, et al. Synergistic effect of all-trans retinoic acid and herpes simplex virus thymidine kinase gene on glioma. Ai Zheng. 2002;21:473–9. (in Chinese) PMID: 12452035.PubMed Zhang XF, Ren ZY, Fang FD, Zuo J, Su CB, Wang RZ, et al. Synergistic effect of all-trans retinoic acid and herpes simplex virus thymidine kinase gene on glioma. Ai Zheng. 2002;21:473–9. (in Chinese) PMID: 12452035.PubMed
17.
Zurück zum Zitat Pollmann MA, Shao Q, Laird DW, Sandig M. Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture. Breast Cancer Res. 2005;7:R522–34. PMID: 15987459.PubMedCrossRef Pollmann MA, Shao Q, Laird DW, Sandig M. Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture. Breast Cancer Res. 2005;7:R522–34. PMID: 15987459.PubMedCrossRef
18.
Zurück zum Zitat Zhang ZQ, Hu Y, Wang BJ, Lin ZX, Naus CC, Nicholson BJ. Effective asymmetry in gap junctional intercellular communication between populations of human normal lung fibroblasts and lung carcinoma cells. Carcinogenesis. 2004;25:473–82. PMID: 14656943.PubMedCrossRef Zhang ZQ, Hu Y, Wang BJ, Lin ZX, Naus CC, Nicholson BJ. Effective asymmetry in gap junctional intercellular communication between populations of human normal lung fibroblasts and lung carcinoma cells. Carcinogenesis. 2004;25:473–82. PMID: 14656943.PubMedCrossRef
19.
Zurück zum Zitat Peebles KA, Duncan MW, Ruch RJ, Malkinson AM. Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1. Carcinogenesis. 2003;24:651–7. PMID:12727792.PubMedCrossRef Peebles KA, Duncan MW, Ruch RJ, Malkinson AM. Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1. Carcinogenesis. 2003;24:651–7. PMID:12727792.PubMedCrossRef
20.
Zurück zum Zitat Willenberg HS, Schott M, Saeger W, Tries A, Scherbaum WA, Bornstein SR. Expression of connexins in chromaffin cells of normal human adrenals and in benign and malignant pheochromocytomas. Ann N Y Acad Sci. 2006;1073:578–83. PMID:17102126.PubMedCrossRef Willenberg HS, Schott M, Saeger W, Tries A, Scherbaum WA, Bornstein SR. Expression of connexins in chromaffin cells of normal human adrenals and in benign and malignant pheochromocytomas. Ann N Y Acad Sci. 2006;1073:578–83. PMID:17102126.PubMedCrossRef
21.
Zurück zum Zitat Kawasaki Y, Kubomoto A, Yamasaki H. Control of intracellular localization and function of Cx43 by SEMA3F. J Mebr Biol. 2007;217:53–61. PMID: 17665084.CrossRef Kawasaki Y, Kubomoto A, Yamasaki H. Control of intracellular localization and function of Cx43 by SEMA3F. J Mebr Biol. 2007;217:53–61. PMID: 17665084.CrossRef
22.
Zurück zum Zitat Hernandez M, Shao Q, Yang XJ, Luh SP, Kandouz M, Batist G, et al. A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells. Prostate. 2006;66:1151–61. PMID: 16652385.PubMedCrossRef Hernandez M, Shao Q, Yang XJ, Luh SP, Kandouz M, Batist G, et al. A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells. Prostate. 2006;66:1151–61. PMID: 16652385.PubMedCrossRef
Metadaten
Titel
Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters
verfasst von
Qi-Lian Liang
Bi-Rong Wang
Guo-Qiang Chen
Guo-Hong Li
Yan-Yun Xu
Publikationsdatum
01.12.2010
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 4/2010
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-009-9354-1

Weitere Artikel der Ausgabe 4/2010

Medical Oncology 4/2010 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.