Galectin-3 and cyclin D1 expression in non-small cell lung cancer

Journal of Experimental & Clinical Cancer Research

Renata Jankowska¹  Marcin Gołecki¹  Aneta Kowal¹  Paweł Piesiak¹  Monika Kosacka¹ 

[1] Chair and Department of Pulmonology and Lung Cancer, Silesian Piasts University of Medicine in Wroclaw, Poland, 53-439 Wroclaw, ul. Grabiszynska 105

关键词: prognostic factor;    non-small cell lung cancer;    cyclin D1;    galectin-3;   

Others  :  827123
DOI  :  10.1186/1756-9966-30-101

 received in 2011-07-11, accepted in 2011-10-24,  发布年份 2011

【 摘 要 】

Introduction

Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC). We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue.

Materials and methods

We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90). years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA) and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA).

Results

Galectin-3 expression was positive in 18 cases (38.29%) and cyclin D1 in 39 (82.97%). We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07) and cyclin D1 expression was higher in this group (p = 0.080). We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi² Yatesa 7.53, p = 0.0061) and we revealed negative correlation between cyclin D1 and galectin-3 expression (R Spearman -0.458, p = 0.0011). In squamous cell lung cancer we didn't observed correlations between these both examinated markers (R = -0.158, p = 0.460), and in adenocarcinoma the negative correlation was very strong (R = -0.829 p = 0.000132).

Conclusions

We didn't reveal any important correlations between clinicopathological findings and galectin-3 and cyclin D1 expression and in non small cell lung cancer. We didn't observed also prognostic value of cyclin D1 or galectin-3 expression. But we showed higher cyclin D1 expression in galectin-3 negative tumor tissues. We revealed also differences in correlations between galectin-3 and cyclin D1 expression in two main histopathological types of NSCLC.

【 授权许可】

   
2011 Kosacka et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Jamal A, Bray F, Center MM, Ferlay J, Ward E, Forman : Global cancer statistics. CA Cancer J Clin 2011, 61(2):69-90.
• [2]Skuladottir H, Olsen JH: Epidemiology of lung cancer. In Lung cancer. Edited by Spiro SG. ERS Journals 2001, Ltd, Sheffield; 1-12.
• [3]Berrino F, De Angelis R, Sant M, Rosso S, Bielska-Lasota M, Coebergh JW, Santaguilani M, EUROCARE Working group : Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study. Lancet Oncol 2007, 8(9):773-783.
• [4]Rumilla KM, Erickson LA, Erickson AK, Lloyd RV: Galectin-4 expression in carcinoid tumors. Endocr Pathol 2006, 17(3):243-249.
• [5]Takenaka Y, Fukumori T, Raz A: Galectin-3 and metastasis. Glycoconi J 2004, 19(7-9):543-549.
• [6]Ingrassia L, Camby I, Lefranc F, Mathieu V, Nshimyumukiza P, Darro F, Kiss R: Anti-galectin compounds as potential anti-cancer drugs. Curr Med Chem 2006, 13(29):3513-3527.
• [7]Fukumori T, Kanayama HO, Raz A: The role of galectin-3 in cancer drug resistance. Drug Resist Updat 2007, 10(3):101-108.
• [8]Mac Lachlan TK, Sang N, Giordano A: Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer. Crit Rev Eukaryot Gene Expr 1995, 5(2):127-156.
• [9]Caputi M, Groeger AM, Esposito V, Dean C, De Luca A, Pacilio C, Muller MR, Giordano GG, Baldia F, Wolner E, Giordano A: Prognostic role of cyclin D1 in lung cancer. Relationship to proliferating cell nuclear antigen. Am J Respir Cell Mol Biol 1999, 20:746-750.
• [10]Jirawatnotai S, Hu Y, Michowski W, Elias JE, Becks L, Bienvenu F, Zagozdzon A, Goswami T, Wang YE, Clark AB, Kunkel TA, van Harn T, Xia B, Correll M, Quackenbush J, Livingston DM, Gygi SP, Sicinski P: A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 2011, 474(7350):230-234.
• [11]Dworakowska D: Rola białka p53, pRB, p21WAF1/CIP1, PCNA, mdm2 oraz cykliny D1 w regulacji cyklu komórkowego oraz apoptozy. Onkol Pol 2005, 8(4):223-228.
• [12]Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Syrjanen K, Kosma VM: Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival. Br J Cancer 1999, 80(12):2001-2007.
• [13]Itami A, Shimada Y, Watanabe G, Imamura M: Prognostic value of p27(Kip1) and CyclinD1 expression in esophageal cancer. Oncology 1999, 57(4):311-317.
• [14]Sato Y, Itoh F, Hareyama M, Satoh M, Hinoda Y, Seto M, Ueda R, Imai K: Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma. J Gastroenterol 1999, 34(4):486-493.
• [15]Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM: Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res 2005, 11:3974-3986.
• [16]Zhu CQ, Shih W, Ling CH, Tsao MS: Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol 2006, 59(8):790-800.
• [17]Au NH, Cheang M, Huntsman DG, Yorida E, Coldman A, Elliot WM, Bebb G, Flint J, English J, Gilks CB, Grimes HL: Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol 2004, 204(1):101-109.
• [18]Szoke T, Kayser K, Trojan I, Kayser G, Furak J, Tiszlavicz L, Baumhakel JD, Gabius HJ: The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II. Eur J Cardiothorac Surg 2007, 31(5):783-787.
• [19]Puglisi F, Minisini AM, Barbone F, Intersimone D, Aprile G, Puppin C, Damante G, Paron I, Tell G, Piga A, Di Loreto C: Galectin-3 expression in non-small cell lung carcinoma. Cancer Lett 2004, 212(2):233-239.
• [20]Mathieu A, Saal I, Vuckovic A, Ransy V, Vereerstraten P, Kaltner H, Gabius HJ, Kiss R, Decaestecker C, Salmon I, Remmelink M: Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung. Mod Pathol 2005, 18(9):1264-1271.
• [21]Hubert M, Wang SY, Wang JL, Seve AP, Hubert J: Intracellular distribution of galectin-3 in mouse 3T3 fibroblasts: comparative analyses by immunofluorescence and immunoelectron microscopy. Exp Cell Res 1995, 220(2):397-406.
• [22]Wu MH, Hong TM, Cheng HW, Pan SH, Liang YR, Hong HC, Chiang WF, Wong TY, Shieh DB, Shieh AL, Jin YT, Chen YL: Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons. Mol Cancer Res 2009, 7(3):311-318.
• [23]Wu ZH, Gan L: Association of galectin-3 and E-cadherin expression with node metastasis of colon cancer. Nan Fang Yi Ke Da Xue Xue Bao 2007, 27(11):1731-1733.
• [24]Liang Y, Li H, Hou SC, Hu B, Miao JB, Li T, You B, Yu LX, Wang L, Chen QR, Chen X: The expression of galectin-3 and osteopontin in occult metastasis of non-small cell lung cancer. Zhonghua Wai Ke Za Zhi 2009, 47(14):1061-1063.
• [25]Mishina T, Dosaka-Akita H, Kinoshita I, Hommura F, Morikawa T, Katoh H, Kawasaki Y: Cyclin D1 expression in non -small-cell lung cancer: its association with altered p53 expression, cell proliferation and clinical outcome. Br J Cancer 1999, 80(8):1289-1295.
• [26]Ayeda AK, Adesina A: Prognostic significance of cyclin D1 expression in resected stage I, II non-small cell lung cancer in Arabs. Interact CardioVasc Thorac Surg 2006, 5:47-51.
• [27]Mohamed S, Yasufuku K, Hiroshima K, Nakajima T, Yoshida S, Suzuki M, Sekine Y, Shibuya K, Iizasa T, Farouk A, Fujisawa T: Prognostic implications of cell cycle-related proteins in primary resectable N2 non-small cell lung cancer. Cancer 2007, 109(12):2506-2514.
• [28]Ferrazzo KL, Neto MM, dos Santos E, dos Santos Pinto D, de Sousa SO: Differential expression of galectin-3, beta-catenin, and cyclin D1 in adenoid cystic carcinoma and polymorphus low-grade adenocarcinoma of salivary glands. J Oral Pathol Med 2009, 38(9):701-707.
• [29]Acikalin MF, Etiz D, Gurbuz MK, Ozudogru E, Canaz F, Colak E: Prognostic significance of galectin-3 and cyclin D1 expression in undifferentiated nasopharyngeal carcinoma. Med Oncol 2011, in press.
• [30]Kim HR, Lin HM, Biliran H, Raz A: Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer Res 1999, 59(16):4148-4154.
• [31]Zhu X, Ohtsubo M, Bohmer RM, Roberts JM, Assojan RK: Adhesion-dependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein. J Cell Biol 1996, 133(2):391-403.
• [32]Mac Kinnon AC, Kopatz J, Sethi T: The molecular and cellular biology of lung cancer: identifying novel therapeutic strategies. Br Med Bull 2010, 95:47-61.