High Levels of Expression of Human Stromal Cell-Derived Factor-1 Are Associated with Worse Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

被引:59
作者
Liang, John J. [2 ]
Zhu, Shaobo [3 ]
Bruggeman, Richard [2 ]
Zaino, Richard J. [2 ]
Evans, Douglas B. [4 ]
Fleming, Jason B. [5 ]
Gomez, Henry F. [5 ]
Zander, Dani S. [2 ]
Wang, Huamin [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Unit 085, Houston, TX 77030 USA
[2] Penn State Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA
[3] Geisinger Med Ctr, Dept Pathol, Danville, PA 17822 USA
[4] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
关键词
BREAST-CANCER METASTASIS; LYMPH-NODE METASTASIS; CHEMOKINE RECEPTOR; LUNG-CANCER; INTRAEPITHELIAL NEOPLASIA; TUMOR-GROWTH; CXCR4; SDF-1; PROGRESSION; MIGRATION;
D O I
10.1158/1055-9965.EPI-10-0405
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, have been shown to mediate invasiveness and metastatic behavior in a number of cancers, including ovarian, prostate, bladder, breast, and pancreatic cancers. The expression and significance of SDF-1 in pancreatic ductal adenocarcinoma (PDA) have not been systematically studied. Methods: We examined the expression of SDF-1 by immunohistochemistry using a mouse anti-human SDF-1/CXCL12 antibody (dilution 1: 300) and a tissue microarray consisting of 72 stage II PDAs from pancreaticoduodenectomy specimens. The staining results were categorized as SDF-1-high (SDF-1-H; cytoplasmic staining of >= 10% of tumor cells) or SDF-1-low (SDF-1-L; no staining or staining of <10% of tumor cells). The results of SDF-1 expression were correlated with clinicopathologic parameters and survival. Statistical analyses were done using SPSS software. Result: Of the 72 stage II PDAs, 25 (35%) showed high levels of SDF-1 expression. The median overall and recurrence-free survival for patients with SDF-1-H PDAs were 26.1 and 11.1 months, respectively, compared with 44.3 and 22.3 months for patients with SDF-1-L tumors (log-rank test, P = 0.047 and P = 0.021). In multivariate analysis, high SDF-1 expression correlated with poor overall and disease-free survival (P = 0.02 and P = 0.02) independent of tumor size, differentiation, and lymph node status. Conclusion: High levels of SDF-1 expression were associated with poor overall and disease-free survival in patients with stage II PDA. SDF-1 may serve as a useful prognostic marker for stage II PDA. Impact: Our results suggest that SDF-1-CXCR4 or SDF-1-CXCR7 pathways may represent a potential target for therapeutic intervention as well as prediction of prognosis in PDA. Cancer Epidemiol Biomarkers Prev; 19(10); 2598-604. (C) 2010 AACR.
引用
收藏
页码:2598 / 2604
页数:7
相关论文
共 38 条
[1]   Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1) [J].
Ara, T ;
Nakamura, Y ;
Egawa, T ;
Sugiyama, T ;
Abe, K ;
Kishimoto, T ;
Matsui, Y ;
Nagasawa, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (09) :5319-5323
[2]   Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy [J].
Askari, AT ;
Unzek, S ;
Popovic, ZB ;
Goldman, CK ;
Forudi, F ;
Kiedrowski, M ;
Rovner, A ;
Ellis, SG ;
Thomas, JD ;
DiCorleto, PE ;
Topol, EJ ;
Penn, MS .
LANCET, 2003, 362 (9385) :697-703
[3]   The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes [J].
Balabanian, K ;
Lagane, B ;
Infantino, S ;
Chow, KYC ;
Harriague, J ;
Moepps, B ;
Arenzana-Seisdedos, F ;
Thelen, M ;
Bachelerie, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (42) :35760-35766
[4]   The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry [J].
Bleul, CC ;
Farzan, M ;
Choe, H ;
Parolin, C ;
ClarkLewis, I ;
Sodroski, J ;
Springer, TA .
NATURE, 1996, 382 (6594) :829-833
[5]   A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) [J].
Bleul, CC ;
Fuhlbrigge, RC ;
Casasnovas, JM ;
Aiuti, A ;
Springer, TA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (03) :1101-1109
[6]   A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development [J].
Burns, Jennifer M. ;
Summers, Bretton C. ;
Wang, Yu ;
Melikian, Anita ;
Berahovich, Rob ;
Miao, Zhenhua ;
Penfold, Mark E. T. ;
Sunshine, Mary Jean ;
Littman, Dan R. ;
Kuo, Calvin J. ;
Wei, Kevin ;
McMaster, Brian E. ;
Wright, Kim ;
Howard, Maureen C. ;
Schall, Thomas J. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (09) :2201-2213
[7]   FREQUENT SOMATIC MUTATIONS AND HOMOZYGOUS DELETIONS OF THE P16 (MTS1) GENE IN PANCREATIC ADENOCARCINOMA [J].
CALDAS, C ;
HAHN, SA ;
DACOSTA, LT ;
REDSTON, MS ;
SCHUTTE, M ;
SEYMOUR, AB ;
WEINSTEIN, CL ;
HRUBAN, RH ;
YEO, CJ ;
KERN, SE .
NATURE GENETICS, 1994, 8 (01) :27-32
[8]   CXCL12/CXCR4 promotes motility and proliferation of glioma cells [J].
do Carmo, Analia ;
Patricio, Ines ;
Cruz, Maria T. ;
Carvalheiro, Helena ;
Oliveira, Catarina R. ;
Lopes, Maria C. .
CANCER BIOLOGY & THERAPY, 2010, 9 (01) :56-65
[9]   The Chemokine Receptors CXCR4 and CXCR3 in Cancer [J].
Fulton, Amy M. .
CURRENT ONCOLOGY REPORTS, 2009, 11 (02) :125-131
[10]   CXCR7 transcription in human non-small cell lung cancer and tumor-free lung tissues; possible regulation upon chemotherapy [J].
Goldmann, Torsten ;
Droemann, Daniel ;
Radtke, Janine ;
Marwitz, Sebastian ;
Lang, Dagmar S. ;
Schultz, Holger ;
Vollmer, Ekkehard .
VIRCHOWS ARCHIV, 2008, 452 (03) :347-348