Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2012

Open Access 01-12-2012 | Research

Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast cancer

Authors: Xiaopeng Cai, Shuai Ma, Ming Gu, Cong Zu, Wenzhi Qu, Xinyu Zheng

Published in: Diagnostic Pathology | Issue 1/2012

Login to get access

Abstract

Background

As a known regulator of apoptosis, survivin has positive relationship with lymphatic metastasis in breast cancer. This study aims to detect the difference in expression between survivin and vascular endothelial growth factor-C (VEGF-C) in treated breast cancer cells and tissues, and to analyze the correlation among survivin, VEGF-C and lymphatic metastasis.

Methods

Plasmid with survivin and VEGF-C shRNA and lentivirus with survivin gene were constructed and transfected into breast cancer cell ZR-75-30. Then the expressions of the two genes were examined using western blot analysis and real-time PCR. The change of invasiveness of breast cancer cells was assessed using matrigel invasion assay. Using immunohistochemistry, the expression of survivin and VEGF-C were analyzed in 108 clinical breast cancer cases with breast cancer tissue and lymph node.

Results

Survivin regulated the expression of VEGF-C at both protein and mRNA levels in breast cancer cells. Immunohistochemical analysis showed that the level of VEGF-C expression was significantly related with that of survivin in breast cancer tissues (p<0.05). VEGF-C was found to participate in the process of breast cancer cells invasion mediated by survivin. The co-expression of the two and the single expression of any one took significant difference in positive lymph node (p<0.05).

Conclusions

Survivin takes an important part in regulating the expression of VEGF-C. VEGF-C could influence the invasive ability mediated by survivin. The co-expression of survivin and VEGF-C is more statistically significant to assess lymphatic metastasis in breast cancer.

Virtual slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​9193530897100952​
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
Fisher B, Bauer M, Wickerham DL, Redmond CK, Fisher ER, Cruz AB, Foster R, Gardner B, Lerner H, Margolese R, et al.: Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer. 1983, 52: 1551-1557. 10.1002/1097-0142(19831101)52:9<1551::AID-CNCR2820520902>3.0.CO;2-3.CrossRefPubMed
3.
Lv N, Xie X, Ge Q, Lin S, Wang X, Kong Y, Shi H, Wei W: Epidermal growth factor receptor in breast carcinoma: association between gene copy number and mutations. Diagn Pathol. 2011, 6: 118-10.1186/1746-1596-6-118.PubMedCentralCrossRefPubMed
4.
Xiang L, Su P, Xia S, Liu Z, Wang Y, Gao P, Zhou G: ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. Diagn Pathol. 2011, 6: 90-10.1186/1746-1596-6-90.PubMedCentralCrossRefPubMed
5.
Ryan BM, O’Donovan N, Duffy MJ: Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009, 35: 553-562. 10.1016/j.ctrv.2009.05.003.CrossRefPubMed
6.
Pennati M, Folini M, Zaffaroni N: Targeting survivin in cancer therapy. Expert Opin Ther Targets. 2008, 12: 463-476. 10.1517/14728222.12.4.463.CrossRefPubMed
7.
Rodel C, Haas J, Groth A, Grabenbauer GG, Sauer R, Rodel F: Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities: survivin as a radioresistance factor. Int J Radiat Oncol Biol Phys. 2003, 55: 1341-1347. 10.1016/S0360-3016(02)04618-7.CrossRefPubMed
8.
Chakravarti A, Zhai GG, Zhang M, Malhotra R, Latham DE, Delaney MA, Robe P, Nestler U, Song Q, Loeffler J: Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms. Oncogene. 2004, 23: 7494-7506. 10.1038/sj.onc.1208049.CrossRefPubMed
9.
Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, Ahmed M, Zakaria J: Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast. Singapore Med J. 2007, 48: 607-614.PubMed
10.
Da CL, Xin Y, Zhao J, Luo XD: Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions. World J Gastroenterol. 2009, 15: 4055-4061. 10.3748/wjg.15.4055.PubMedCentralCrossRefPubMed
11.
Kim YH, Kim SM, Kim YK, Hong SP, Kim MJ, Myoung H: Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma. J Oral Pathol Med. 2010, 39: 368-375.PubMed
12.
Su L, Wang Y, Xiao M, Lin Y, Yu L: Up-regulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010, 110: 484-491. 10.1016/j.tripleo.2010.04.009.CrossRefPubMed
13.
Xiaoyuan C, Longbang C, Jinghua W, Xiaoxiang G, Huaicheng G, Qun Z, Haizhu S: Survivin: a potential prognostic marker and chemoradiotherapeutic target for colorectal cancer. Ir J Med Sci. 2010, 179: 327-335. 10.1007/s11845-009-0448-8.CrossRefPubMed
14.
Lohela M, Bry M, Tammela T, Alitalo K: VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr Opin Cell Biol. 2009, 21: 154-165. 10.1016/j.ceb.2008.12.012.CrossRefPubMed
15.
Guo B, Zhang Y, Luo G, Li L, Zhang J: Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma. Anat Rec (Hoboken). 2009, 292: 633-639. 10.1002/ar.20893.CrossRef
16.
Achen MG, Stacker SA: Molecular control of lymphatic metastasis. Ann N Y Acad Sci. 2008, 1131: 225-234. 10.1196/annals.1413.020.CrossRefPubMed
17.
Tanaka T, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, Shiozaki M, Naganawa Y, Fujii Y, Takeyama H: Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res. 2010, 29: 83-10.1186/1756-9966-29-83.PubMedCentralCrossRefPubMed
18.
Ran S, Volk L, Hall K, Flister MJ: Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology. 2010, 17: 229-251. 10.1016/j.pathophys.2009.11.003.PubMedCentralCrossRefPubMed
19.
Feng Y, Wang W, Hu J, Ma J, Zhang Y, Zhang J: Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer. Anat Rec (Hoboken). 2010, 293: 802-812. 10.1002/ar.21096.CrossRef
20.
Zhang C, Hao L, Wang L, Xiao Y, Ge H, Zhu Z, Luo Y, Zhang Y: Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer. BMC Cancer. 2010, 10: 184-10.1186/1471-2407-10-184.PubMedCentralCrossRefPubMed
21.
Eibl G, Bruemmer D, Okada Y, Duffy JP, Law RE, Reber HA, Hines OJ: PGE(2) is generated by specific COX-2 activity and increases VEGF production in COX-2-expressing human pancreatic cancer cells. Biochem Biophys Res Commun. 2003, 306: 887-897. 10.1016/S0006-291X(03)01079-9.CrossRefPubMed
22.
Hsieh CY, Chen CA, Chou CH, Lai KP, Jeng YM, Kuo ML, Wei LH: Overexpression of Her-2/NEU in epithelial ovarian carcinoma induces vascular endothelial growth factor C by activating NF-kappa B: implications for malignant ascites formation and tumor lymphangiogenesis. J Biomed Sci. 2004, 11: 249-259.PubMed
23.
Su JL, Shih JY, Yen ML, Jeng YM, Chang CC, Hsieh CY, Wei LH, Yang PC, Kuo ML: Cyclooxygenase-2 induces EP1- and HER-2/Neu-dependent vascular endothelial growth factor-C up-regulation: a novel mechanism of lymphangiogenesis in lung adenocarcinoma. Cancer Res. 2004, 64: 554-564. 10.1158/0008-5472.CAN-03-1301.CrossRefPubMed
24.
Yang Y, Zhu J, Gou H, Cao D, Jiang M, Hou M: Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC). Med Oncol. 2011, 28: 796-803. 10.1007/s12032-010-9519-y.CrossRefPubMed
25.
Yildirim U, Erdem H, Kayikci A, Sahin AF, Uzunlar AK, Albayrak A: Cyclooxygenase-2 and survivin in superficial urothelial carcinoma of the bladder and correlation with intratumoural microvessel density. J Int Med Res. 2010, 38: 1689-1699.CrossRefPubMed
26.
Lambropoulou M, Papadopoulos N, Tripsianis G, Alexiadis G, Pagonopoulou O, Kiziridou A, Liberis V, Kakolyris S, Chatzaki E: Co-expression of survivin, c-erbB2, and cyclooxygenase-2 (COX-2): prognostic value and survival of endometrial cancer patients. J Cancer Res Clin Oncol. 2010, 136: 427-435. 10.1007/s00432-009-0673-6.CrossRefPubMed
27.
Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC: IAP regulation of metastasis. Cancer Cell. 2010, 17: 53-64. 10.1016/j.ccr.2009.11.021.PubMedCentralCrossRefPubMed
28.
Khan S, Aspe JR, Asumen MG, Almaguel F, Odumosu O, Acevedo-Martinez S, De Leon M, Langridge WH, Wall NR: Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. Br J Cancer. 2009, 100: 1073-1086. 10.1038/sj.bjc.6604978.PubMedCentralCrossRefPubMed
29.
Issa A, Le TX, Shoushtari AN, Shields JD, Swartz MA: Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype. Cancer Res. 2009, 69: 349-357. 10.1158/0008-5472.CAN-08-1875.CrossRefPubMed
30.
Chen Y, Jiang L, She F, Tang N, Wang X, Li X, Han S, Zhu J: Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism. Mol Cell Biochem. 2010, 345: 77-89. 10.1007/s11010-010-0562-y.CrossRefPubMed
31.
Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001, 7: 192-198. 10.1038/84643.CrossRefPubMed
32.
Koyama Y, Kaneko K, Akazawa K, Kanbayashi C, Kanda T, Hatakeyama K: Vascular endothelial growth factor-C and vascular endothelial growth factor-d messenger RNA expression in breast cancer: association with lymph node metastasis. Clin Breast Cancer. 2003, 4: 354-360. 10.3816/CBC.2003.n.041.CrossRefPubMed
33.
Yie SM, Luo B, Ye NY, Xie K, Ye SR: Detection of Survivin-expressing circulating cancer cells in the peripheral blood of breast cancer patients by a RT-PCR ELISA. Clin Exp Metastasis. 2006, 23: 279-289. 10.1007/s10585-006-9037-7.CrossRefPubMed
Metadata
Title
Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast cancer
Authors
Xiaopeng Cai
Shuai Ma
Ming Gu
Cong Zu
Wenzhi Qu
Xinyu Zheng
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2012
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-7-52

Other articles of this Issue 1/2012

Diagnostic Pathology 1/2012 Go to the issue

Case Report

CD20-positive NK/T-cell lymphoma with indolent clinical course: report of case and review of literature

Research

Brain MRI and biological diagnosis in five Tunisians MLD patients

Case Report

Peripheral T-cell Lymphoma with Cyclin D1 overexpression: a case report

Case Report

A case of Arrhythmogenic right ventricular cardiomyopathy without arrhythmias

Research

EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence

Case Report

Postoperative lumbar spinal stenosis after intertransverse fusion with granules of hydroxyapatite: a case report