This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Negus, R. P. Articles by Balkwill, F. R. Search for Related Content PubMed PubMed Citation Articles by Negus, R. P. Articles by Balkwill, F. R.

American Journal of Pathology, Vol 150, 1723-1734, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines

RP Negus, GW Stamp, J Hadley and FR Balkwill
Biological Therapies Laboratory, Imperial Cancer Research Fund, London, United Kingdom.

We have defined the host leukocyte infiltrate in epithelial ovarian tumors and related this to the expression of C-C chemokines. Immunohistochemical analysis of 20 paraffin-embedded biopsies showed that the infiltrate was primarily composed of CD68+ macrophages and CD8+/CD45RO+ T cells (median values, 3700 cells/mm3 and 2200 cells/mm3, respectively). Natural killer cells, B cells, and mast cells occurred in lower numbers (median values, 0 to 200 cells/mm3). Eosinophils were rarely seen and neutrophils were mainly confined to blood vessels. More infiltrating cells were found in stromal than in tumor areas. Only macrophages occurred in significant numbers in areas of necrosis (P < 0.0005). Using in situ hybridization to mRNA, we examined expression of the chemokines MCP-1, MIP-1 alpha, MIP-1 beta, and RANTES. MCP-1 and MIP-1 alpha were expressed by significantly more cells than MIP-1 beta and RANTES (P < 0.005). In tumor epithelial areas, the predominant chemokine was MCP-1. MCP-1 and MIP-1 alpha were the predominant stromal chemokines. A significant correlation was found between the total number of CD8+ T cells and the number of cells expressing MCP-1 (rs = 0.63 and P < 0.003, respectively) and between the CD8+ population and RANTES-expressing cells (rs = 0.6 and P < 0.003). A correlation was also found between CD68+ macrophages and the number of cells expressing MCP-1 (rs = 0.50 and P = 0.026). We suggest that MCP-1 may be responsible for the leukocyte infiltrate in ovarian carcinomas, but the expression of other chemokines may determine its exact nature.

This article has been cited by other articles:

				C. Guruvayoorappan Tumor Versus Tumor-Associated Macrophages: How Hot is the Link? Integr Cancer Ther, June 1, 2008; 7(2): 90 - 95. [Abstract] [PDF]

				C. Murdoch, S. Tazzyman, S. Webster, and C. E. Lewis Expression of Tie-2 by Human Monocytes and Their Responses to Angiopoietin-2 J. Immunol., June 1, 2007; 178(11): 7405 - 7411. [Abstract] [Full Text] [PDF]

				A. Barber, T. Zhang, L. R. DeMars, J. Conejo-Garcia, K. F. Roby, and C. L. Sentman Chimeric NKG2D Receptor-Bearing T Cells as Immunotherapy for Ovarian Cancer Cancer Res., May 15, 2007; 67(10): 5003 - 5008. [Abstract] [Full Text] [PDF]

				T. Hagemann, J. Wilson, F. Burke, H. Kulbe, N. F. Li, A. Pluddemann, K. Charles, S. Gordon, and F. R. Balkwill Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol., April 15, 2006; 176(8): 5023 - 5032. [Abstract] [Full Text] [PDF]

				T. Kakinuma and S. T. Hwang Chemokines, chemokine receptors, and cancer metastasis J. Leukoc. Biol., April 1, 2006; 79(4): 639 - 651. [Abstract] [Full Text] [PDF]

				C. E. Lewis and J. W. Pollard Distinct Role of Macrophages in Different Tumor Microenvironments Cancer Res., January 15, 2006; 66(2): 605 - 612. [Abstract] [Full Text] [PDF]

				S. Madhusudan, S. R. Muthuramalingam, J. P. Braybrooke, S. Wilner, K. Kaur, C. Han, S. Hoare, F. Balkwill, and T. S. Ganesan Study of Etanercept, a Tumor Necrosis Factor-Alpha Inhibitor, in Recurrent Ovarian Cancer J. Clin. Oncol., September 1, 2005; 23(25): 5950 - 5959. [Abstract] [Full Text] [PDF]

				C. Lewis and C. Murdoch Macrophage Responses to Hypoxia: Implications for Tumor Progression and Anti-Cancer Therapies Am. J. Pathol., September 1, 2005; 167(3): 627 - 635. [Abstract] [Full Text] [PDF]

				G. V. Shurin, R. Ferris, I. L. Tourkova, L. Perez, A. Lokshin, L. Balkir, B. Collins, G. S. Chatta, and M. R. Shurin Loss of New Chemokine CXCL14 in Tumor Tissue Is Associated with Low Infiltration by Dendritic Cells (DC), while Restoration of Human CXCL14 Expression in Tumor Cells Causes Attraction of DC Both In Vitro and In Vivo J. Immunol., May 1, 2005; 174(9): 5490 - 5498. [Abstract] [Full Text] [PDF]

				T. Zhang, R. Somasundaram, K. Berencsi, L. Caputo, P. Rani, D. Guerry, E. Furth, B. J. Rollins, M. Putt, P. Gimotty, et al. CXC Chemokine Ligand 12 (Stromal Cell-Derived Factor 1{alpha}) and CXCR4-Dependent Migration of CTLs toward Melanoma Cells in Organotypic Culture J. Immunol., May 1, 2005; 174(9): 5856 - 5863. [Abstract] [Full Text] [PDF]

				P. Allavena, M. Signorelli, M. Chieppa, E. Erba, G. Bianchi, F. Marchesi, C. O. Olimpio, C. Bonardi, A. Garbi, A. Lissoni, et al. Anti-inflammatory Properties of the Novel Antitumor Agent Yondelis (Trabectedin): Inhibition of Macrophage Differentiation and Cytokine Production Cancer Res., April 1, 2005; 65(7): 2964 - 2971. [Abstract] [Full Text] [PDF]

				M. R. Raspollini, F. Castiglione, D. Rossi Degl'Innocenti, G. Amunni, A. Villanucci, F. Garbini, G. Baroni, and G. L. Taddei Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma Ann. Onc., April 1, 2005; 16(4): 590 - 596. [Abstract] [Full Text] [PDF]

				F. Marchesi, P. Monti, B. E. Leone, A. Zerbi, A. Vecchi, L. Piemonti, A. Mantovani, and P. Allavena Increased Survival, Proliferation, and Migration in Metastatic Human Pancreatic Tumor Cells Expressing Functional CXCR4 Cancer Res., November 15, 2004; 64(22): 8420 - 8427. [Abstract] [Full Text] [PDF]

				C. Murdoch, A. Giannoudis, and C. E. Lewis Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues Blood, October 15, 2004; 104(8): 2224 - 2234. [Abstract] [Full Text] [PDF]

				M. R. Zielinski, M. Muenchow, M. A. Wallig, P. L. Horn, and J. A. Woods Exercise delays allogeneic tumor growth and reduces intratumoral inflammation and vascularization J Appl Physiol, June 1, 2004; 96(6): 2249 - 2256. [Abstract] [Full Text] [PDF]

				K. Kawada, M. Sonoshita, H. Sakashita, A. Takabayashi, Y. Yamaoka, T. Manabe, K. Inaba, N. Minato, M. Oshima, and M. M. Taketo Pivotal Role of CXCR3 in Melanoma Cell Metastasis to Lymph Nodes Cancer Res., June 1, 2004; 64(11): 4010 - 4017. [Abstract] [Full Text] [PDF]

				S. C. Robinson, K. A. Scott, J. L. Wilson, R. G. Thompson, A. E. I. Proudfoot, and F. R. Balkwill A Chemokine Receptor Antagonist Inhibits Experimental Breast Tumor Growth Cancer Res., December 1, 2003; 63(23): 8360 - 8365. [Abstract] [Full Text] [PDF]

				P. Monti, B. E. Leone, F. Marchesi, G. Balzano, A. Zerbi, F. Scaltrini, C. Pasquali, G. Calori, F. Pessi, C. Sperti, et al. The CC Chemokine MCP-1/CCL2 in Pancreatic Cancer Progression: Regulation of Expression and Potential Mechanisms of Antimalignant Activity Cancer Res., November 1, 2003; 63(21): 7451 - 7461. [Abstract] [Full Text] [PDF]

				L. Zhang, J. R. Conejo-Garcia, D. Katsaros, P. A. Gimotty, M. Massobrio, G. Regnani, A. Makrigiannakis, H. Gray, K. Schlienger, M. N. Liebman, et al. Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer N. Engl. J. Med., January 16, 2003; 348(3): 203 - 213. [Abstract] [Full Text] [PDF]

				R. Hernan, R. Fasheh, C. Calabrese, A. J. Frank, K. H. Maclean, D. Allard, R. Barraclough, and R. J. Gilbertson ERBB2 Up-Regulates S100A4 and Several other Prometastatic Genes in Medulloblastoma Cancer Res., January 1, 2003; 63(1): 140 - 148. [Abstract] [Full Text] [PDF]

				C. J. Moran, D. A. Arenberg, C.-C. Huang, T. J. Giordano, D. G. Thomas, D. E. Misek, G. Chen, M. D. Iannettoni, M. B. Orringer, S. Hanash, et al. RANTES Expression Is a Predictor of Survival in Stage I Lung Adenocarcinoma Clin. Cancer Res., December 1, 2002; 8(12): 3803 - 3812. [Abstract] [Full Text] [PDF]

				C. J. Scotton, J. L. Wilson, K. Scott, G. Stamp, G. D. Wilbanks, S. Fricker, G. Bridger, and F. R. Balkwill Multiple Actions of the Chemokine CXCL12 on Epithelial Tumor Cells in Human Ovarian Cancer Cancer Res., October 15, 2002; 62(20): 5930 - 5938. [Abstract] [Full Text] [PDF]

				T. Riman, P. W. Dickman, S. Nilsson, N. Correia, H. Nordlinder, C. M. Magnusson, and I. R. Persson Risk Factors for Invasive Epithelial Ovarian Cancer: Results from a Swedish Case-Control Study Am. J. Epidemiol., August 15, 2002; 156(4): 363 - 373. [Abstract] [Full Text] [PDF]

				Y. Uekusa, W.-G. Yu, T. Mukai, P. Gao, N. Yamaguchi, M. Murai, K. Matsushima, S. Obika, T. Imanishi, Y. Higashibata, et al. A Pivotal Role for CC Chemokine Receptor 5 in T-Cell Migration to Tumor Sites Induced by Interleukin 12 Treatment in Tumor-bearing Mice Cancer Res., July 1, 2002; 62(13): 3751 - 3758. [Abstract] [Full Text] [PDF]

				E. Schutyser, S. Struyf, P. Proost, G. Opdenakker, G. Laureys, B. Verhasselt, L. Peperstraete, I. Van de Putte, A. Saccani, P. Allavena, et al. Identification of Biologically Active Chemokine Isoforms from Ascitic Fluid and Elevated Levels of CCL18/Pulmonary and Activation-regulated Chemokine in Ovarian Carcinoma J. Biol. Chem., June 28, 2002; 277(27): 24584 - 24593. [Abstract] [Full Text] [PDF]

				D. Milliken, C. Scotton, S. Raju, F. Balkwill, and J. Wilson Analysis of Chemokines and Chemokine Receptor Expression in Ovarian Cancer Ascites Clin. Cancer Res., April 1, 2002; 8(4): 1108 - 1114. [Abstract] [Full Text] [PDF]

				E. Azenshtein, G. Luboshits, S. Shina, E. Neumark, D. Shahbazian, M. Weil, N. Wigler, I. Keydar, and A. Ben-Baruch The CC Chemokine RANTES in Breast Carcinoma Progression: Regulation of Expression and Potential Mechanisms of Promalignant Activity Cancer Res., February 1, 2002; 62(4): 1093 - 1102. [Abstract] [Full Text] [PDF]

				T. Onita, P. G. Ji, J. W. Xuan, H. Sakai, H. Kanetake, P. H. Maxwell, G.-H. Fong, M. Y Gabril, M. Moussa, and J. L. Chin Hypoxia-induced, Perinecrotic Expression of Endothelial Per-ARNT-Sim Domain Protein-1/Hypoxia-inducible Factor-2{alpha} Correlates with Tumor Progression, Vascularization, and Focal Macrophage Infiltration in Bladder Cancer Clin. Cancer Res., February 1, 2002; 8(2): 471 - 480. [Abstract] [Full Text] [PDF]

				J. Vakili, L. Standker, M. Detheux, G. Vassart, W.-G. Forssmann, and M. Parmentier Urokinase Plasminogen Activator and Plasmin Efficiently Convert Hemofiltrate CC Chemokine 1 into Its Active [9-74] Processed Variant J. Immunol., September 15, 2001; 167(6): 3406 - 3413. [Abstract] [Full Text] [PDF]

				C. J. Scotton, J. L. Wilson, D. Milliken, G. Stamp, and F. R. Balkwill Epithelial Cancer Cell Migration: A Role for Chemokine Receptors? Cancer Res., July 1, 2001; 61(13): 4961 - 4965. [Abstract] [Full Text] [PDF]

				B. Cambien, M. Pomeranz, M.-A. Millet, B. Rossi, and A. Schmid-Alliana Signal transduction involved in MCP-1-mediated monocytic transendothelial migration Blood, January 15, 2001; 97(2): 359 - 366. [Abstract] [Full Text] [PDF]

				J. K. Sandhu, H. F. Privora, G. Wenckebach, and H. C. Birnboim Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model Am. J. Pathol., February 1, 2000; 156(2): 509 - 518. [Abstract] [Full Text] [PDF]

				F. R. Balkwill Re: Possible Role of Ovarian Epithelial Inflammation in Ovarian Cancer J Natl Cancer Inst, January 19, 2000; 92(2): 162a - 163a. [Full Text] [PDF]

				Z. Duan, A. J. Feller, R. T. Penson, Bruce. A. Chabner, and M. V. Seiden Discovery of Differentially Expressed Genes Associated with Paclitaxel Resistance Using cDNA Array Technology: Analysis of Interleukin (IL) 6, IL-8, and Monocyte Chemotactic Protein 1 in the Paclitaxel-resistant Phenotype Clin. Cancer Res., November 1, 1999; 5(11): 3445 - 3453. [Abstract] [Full Text] [PDF]

				G. Luboshits, S. Shina, O. Kaplan, S. Engelberg, D. Nass, B. Lifshitz-Mercer, S. Chaitchik, I. Keydar, and A. Ben-Baruch Elevated Expression of the CC Chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Advanced Breast Carcinoma Cancer Res., September 1, 1999; 59(18): 4681 - 4687. [Abstract] [Full Text] [PDF]