Diagnostic Pathology | |
Overexpression of both platelet-derived growth factor-BB and vascular endothelial growth factor-C and its association with lymphangiogenesis in primary human non-small cell lung cancer | |
Yuping Sun3  Pei Zhang3  Juan Li3  Liyun Qiu1  Chuanyong Liu3  Jiannan Liu2  | |
[1] Department of Pharmacology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China;Department of Oncology, Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China;Department of Oncology, Jinan Central Hospital, Affiliated to Shandong University, No. 105.Jiefang Road, Jinan, Shandong 250013, P.R. China | |
关键词: Non-small cell lung cancer; Lymphatic micro-vessel density; Vascular endothelial growth factor-C; Platelet-derived growth factor-BB; | |
Others : 1092972 DOI : 10.1186/1746-1596-9-128 |
|
received in 2014-04-01, accepted in 2014-06-13, 发布年份 2014 | |
【 摘 要 】
Background
Metastatic spread of tumor through lymphatic vasculature is an important adverse prognostic factor in a variety of human cancer and tumor lymphangiogenesis requires the interplay of several growth factors. Platelet-derived growth factor (PDGF)-BB and vascular endothelial growth factor (VEGF)-C are two important molecules involving in tumor metastasis and lymphangiogenesis. Therefore, the aim of this study was to investigate the coexpression of PDGF-BB and VEGF-C in primary human non-small cell lung cancer (NSCLC) and its association with lymphangiogenesis.
Methods
Using immunohistochemical staining, PDGF-BB and VEGF-C expression were detected in 109 primary NSCLC tissues, while the lymphatic micro-vessel density (LMVD) was counted.
Results
Of 109 cases, PDGF-BB and VEGF-C overexpression was 66.97% (73/109) and 65.14% (71/109), respectively. 52 (47.7%) had overexpression of both PDGF-BB and VEGF-C (P + V+), 21 (19.3%) overexpression of PDGF-BB but low expression of VEGF-C (P + V-), 19(17.4%) overexpression of VEGF-C but low expression of PDGF-BB (P-V+) and 17(15.6%) low expression of both PDGF-BB and VEGF-C (P-V-). PDGF-BB expression was positively related to that of VEGF-C (r = 0.451, p = 0.034). LMVD in cases with P + V + was much higher than those with P-V- (p = 0.004). In addition, the patients with P + V + were younger and also had larger tumor size, more likely lymph node metastasis and worse histological differentiation than those with P-V-. Moreover, the overall survival (OS) of patients with P + V + was shorter than those with P-V- (p = 0.015).
Conclusion
Coexpression of both PDGF-BB and VEGF-C was associated with lymphangiogenesis and poor prognosis in NSCLC, and might play a critical role in NSCLC progression.
【 授权许可】
2014 Liu et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150130155244521.pdf | 1362KB | download | |
Figure 4. | 54KB | Image | download |
Figure 3. | 49KB | Image | download |
Figure 2. | 50KB | Image | download |
Figure 1. | 252KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]She J, Yang P, Hong Q, Bai C: Lung cancer in china: challenges and interventions. Chest 2013, 143(4):1117-1126.
- [2]Lu Q, Lu S, Huang L, Wang T, Wan Y, Zhou C, Zhang C, Zhang Z, Li X: The expression of V-ATPase is associated with drug resistance and pathology of non-small-cell lung cancer. Diagn Pathol 2013, 8:145.
- [3]Pfannschmidt J, Muley T, Bülzebruck H, Hoffmann H, Dienemann H: Prognostic assessment after surgical resection for non-small cell lung cancer: experiences in 2083 patients. Lung Cancer 2007, 55(3):371.
- [4]Goya T, Asamura H, Yoshimura H, Kato H, Shimokata K, Tsuchiya R, Sohara Y, Miya T, Miyaoka E: Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study. Lung Cancer 2005, 50(2):227-234.
- [5]Christiansen A, Detmar M: Lymphangiogenesis and cancer. Genes Cancer 2011, 2(12):1146-1158.
- [6]El-Gohary YM, Metwally G, Saad RS, Robinson MJ, Mesko T, Poppiti RJ: Prognostic significance of intratumoral and peritumoral lymphatic density and blood vessel density in invasive breast carcinomas. Am J Clin Pathol 2008, 129(4):578-586.
- [7]Karadayι N, Kandemιr NO, Yavuzer D, Korkmaz T, Gecmen G, Kokturk F: Inducible nitric oxide synthase expression in gastric adenocarcinoma: impact on lymphangiogenesis and lymphatic metastasis. Diagn Pathol 2013, 8:151.
- [8]Schoppmann SF, Bayer G, Aumayr K, Taucher S, Geleff S, Rudas M, Kubista E, Hausmaninger H, Samonigg H, Gnant M: Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg 2004, 240(2):306.
- [9]Valencak J, Heere-Ress E, Kopp T, Schoppmann S, Kittler H, Pehamberger H: Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanoma. Eur J Cancer 2004, 40(3):358-364.
- [10]Renyi-Vamos F, Tovari J, Fillinger J, Timar J, Paku S, Kenessey I, Ostoros G, Agocs L, Soltesz I, Dome B: Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non–small cell lung cancer. Clin Canc Res 2005, 11(20):7344-7353.
- [11]Takanami I: Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer. Oncol Rep 2006, 15(2):437-442.
- [12]Zorgetto VA, Silveira GG, Oliveira-Costa JP, Soave DF, Soares FA, Ribeiro-Silva A: The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas. Diagn Pathol 2013, 8(1):170.
- [13]Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K: A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996, 15(2):290.
- [14]Chen J-C, Chang Y-W, Hong C-C, Yu Y-H, Su J-L: The role of the VEGF-C/VEGFRs axis in tumor progression and therapy. Int J Mol Sci 2012, 14(1):88-107.
- [15]Kinoshita J, Kitamura K, Kabashima A, Saeki H, Tanaka S, Sugimachi K: Clinical significance of vascular endothelial growth factor‒C (VEGF‒C) in breast cancer. Breast Canc Res Treat 2001, 66(2):159-164.
- [16]Cai X, Ma S, Gu M, Zu C, Qu W, Zheng X: Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast cancer. Diagn Pathol 2012, 7(1):1-8.
- [17]Kigure W, Fujii T, Sutoh T, Morita H, Katoh T, Yajima R, Yamaguchi S, Tsutsumi S, Asao T, Kuwano H: The Association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor. Hepatogastroenterology 2012, 60(122):277-280.
- [18]Arinaga M, Noguchi T, Takeno S, Chujo M, Miura T, Uchida Y: Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer 2003, 97(2):457-464.
- [19]Cao Y: Direct role of PDGF-BB in lymphangiogenesis and lymphatic metastasis. Cell Cycle 2005, 4(2):231-233.
- [20]Heldin C-H, Eriksson U, Östman A: New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys 2002, 398(2):284-290.
- [21]Cao Y: Emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nat Rev Canc 2005, 5(9):735-743.
- [22]Onimaru M, Yonemitsu Y, Fujii T, Tanii M, Nakano T, Nakagawa K, Kohno R-i, Hasegawa M, Nishikawa S-i, Sueishi K: VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B. Am J Physiol Heart Circ Physiol 2009, 297(5):H1685-H1696.
- [23]Matsumoto S, Yamada Y, Narikiyo M, Ueno M, Tamaki H, Miki K, Wakatsuki K, Enomoto K, Yokotani T, Nakajima Y: Prognostic significance of platelet-derived growth factor-BB expression in human esophageal squamous cell carcinomas. Anticancer Res 2007, 27(4B):2409-2414.
- [24]Donnem T, Al-Saad S, Al-Shibli K, Busund L-T, Bremnes R: Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer. Ann Oncol 2010, 21(2):223-231.
- [25]Fleming ID, Phillips JL, Menck HR, Murphy GP, Winchester DP: The National Cancer Data Base report on recent hospital cancer program progress toward complete American Joint Committee on Cancer/TNM staging. Cancer 1997, 80(12):2305-2310.
- [26]Hensing TA: Clinical evaluation and staging of patients who have lung cancer. Hematol Oncol Clin North Am 2005, 19(2):219-235.
- [27]Hasina R, Whipple ME, Martin LE, Kuo WP, Ohno-Machado L, Lingen MW: Angiogenic heterogeneity in head and neck squamous cell carcinoma: biological and therapeutic implications. Lab Investig 2008, 88(4):342-353.
- [28]Weidner N, Semple JP, Welch WR, Folkman J: Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. New Engl J Med 1991, 324(1):1-8.
- [29]Fidler IJ: The pathogenesis of cancer metastasis: the’seed and soil’hypothesis revisited. Nat Rev Canc 2003, 3(6):453-458.
- [30]Kerjaschki D, Bago-Horvath Z, Rudas M, Sexl V, Schneckenleithner C, Wolbank S, Bartel G, Krieger S, Kalt R, Hantusch B: Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse. J Clin Investig 2011, 121(5):2000.
- [31]Padera TP, Stoll BR, Tooredman JB, Capen D, di Tomaso E, Jain RK: Cancer cells compress intratumour vessels. Nature 2004, 427(6976):695.
- [32]Bono P, Wasenius V-M, Heikkilä P, Lundin J, Jackson DG, Joensuu H: High LYVE-1–positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Canc Res 2004, 10(21):7144-7149.
- [33]Padera TP, Kadambi A, di Tomaso E, Carreira CM, Brown EB, Boucher Y, Choi NC, Mathisen D, Wain J, Mark EJ: Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002, 296(5574):1883-1886.
- [34]Cao R, Björndahl MA, Religa P, Clasper S, Garvin S, Galter D, Meister B, Ikomi F, Tritsaris K, Dissing S: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell 2004, 6(4):333-345.
- [35]Schoppmann SF, Alidzanovic L, Schultheis A, Perkmann T, Brostjan C, Birner P: Thrombocytes correlate with lymphangiogenesis in human esophageal cancer and mediate growth of lymphatic endothelial cells in vitro. PLoS One 2013, 8(6):e66941.
- [36]Shibuya M: Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis A Crucial Target for Anti-and Pro-Angiogenic Therapies. Genes Canc 2011, 2(12):1097-1105.