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01-05-2008 | Original Article

Migration deficit in monocyte-macrophages in human ovarian cancer

Authors: Ralph S. Freedman, Qing Ma, Ena Wang, Stacie T. Gallardo, Ilyssa O. Gordon, Jeong Won Shin, Ping Jin, David Stroncek, Francesco M. Marincola

Published in: Cancer Immunology, Immunotherapy | Issue 5/2008

Abstract

Purpose

To examine the migration responses of monocyte/macrophages (MO/MA) expressing complementary receptors to chemokines produced in the tumor environment of epithelial ovarian cancer (EOC).

Methods

We examined the expression of the chemokine receptors, CCR1, CCR5, and CXCR4, on EOC associated ascitic and blood MO/MA; their response to complementary chemokines in a MO/MA migration assay and the F-actin content in an actin polymerization assay. A validated cDNA microarray assay was then utilized to examine alterations in pathway genes that can be identified with cell migration.

Results

Ascitic and EOC blood MO/MA express CCR1, CCR5 and CXCR4, but differently. Cell surface expression levels for CCR1 and CCR5 were higher in ascites than that of normal blood in contrast to CXCR4 levels in ascitic MO/MA which were lower. EOC associated ascitic or blood MO/MA failed to migrate in response to the CC ligand RANTES and to the CXCR4 reactive chemokine, SDF1 (CXCL12). Ascitic and most EOC blood MO/MA also behaved differently from normal blood MO in the polymerization/depolymerization assay. A cDNA gene analysis of purified ascitic MO/MA demonstrated that a number of genes involved with chemokine production, focal adhesion, actin cytoskeletal function and leukocyte transendothelial migration were down-regulated in the ascitic MO/MA when compared to normal blood MO. Moreover, PBMC cDNA from EOC patients’ blood also showed gene profiles similar to that of ascitic MO/MA.

Conclusions

Defective migration and polymerization/depolymerization activity of MO/MA from EOC patients and a significant down-regulation of critical pathway genes suggest that other mechanisms might be involved in the accumulation of systemically derived MO at the tumor site of EOC patients.

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Piccart M, Bertelsen K, Stuart G, Cassidy J, Mangioni C, Simonsen E, James K, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson R, Swenerton K, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy J-A, Lhoas F, Lidvall B, Bacon M, Birt A, Andersen J, Zee B, Paul J, Pecorelli S, Baron B, McGuire W (2003) Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Int J Gynecol Cancer 13(Suppl 2):144–148PubMedCrossRef

Wang X, Deavers M, Patenia R, Bassett RL, Mueller P, Ma Q, Wang E, Freedman RS (2006) Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Trans Med 4:30CrossRef

Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555PubMedCrossRef

Balkwill F, Ward B, Moodie E (1987) Therapeutic potential of tumor necrosis factor-α and r-interferon in experimental human ovarian cancer. Cancer Res 47:4755–4758PubMed

Colombo MP, Mantovani A (2005) Targeting myelomonocytic cells to revert inflammation-dependent cancer promotion. Cancer Res 65(20):9113–9116PubMedCrossRef

Balkwill FR, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545PubMedCrossRef

Chambers S, Kacinski B, Ivins C, Carcangiu M (1997) Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1. Clin Cancer Res 3:999–1007PubMed

Kacinski B (1995) CSF-1 and its receptor in ovarian, endometrial and breast cancer. Ann Med 27:79–85PubMedCrossRef

Xu FJ, Ramakrishnan S, Daly L, Soper JT, Berchuck A, Clarke-Pearson D, Bast RCJ (1991) Increased serum levels of macrophage colony-stimulating factor in ovarian cancer. Am J Obstet Gynecol 165:1356–1362PubMed

10.

Price F, Chambers S, Chambers J, Carcangiu M, Schwartz P, Kohorn E, Stanley E, Kacinski B (1993) Colony-stimulating factor-1 in primary ascites in ovarian cancer is a significant predictor of survival. Am J Obstet Gynecol 168:520–527PubMed

11.

Kassim SK, El-Salahy EM, Fayed ST, Helal SA, Helal T, Azzam E-D, Khalifa A (2004) Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin Biochem 37(5):363–369PubMedCrossRef

12.

Loercher AE, Nash MA, Kavanagh JJ, Platsoucas CD, Freedman RS (1999) Identification of an IL-10 producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 163:6251–6260PubMed

13.

Gordon IO, Freedman RS (2006) Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients. Clin Cancer Res 12(5):1515–1524PubMedCrossRef

14.

Wang E, Ngalame Y, Panelli MC, Nguyen-Jackson H, Deavers M, Mueller P, Hu W, Savary C, Kobayashi R, Freedman RS, Marincola FM (2005) Peritoneal and sub-peritoneal stroma may facilitate regional spread of ovarian cancer. Clin Cancer Res 11(1):113–122PubMedCrossRef

15.

Melchers F, Rolink A, Schaniel C (1999) The role of chemokines in regulating cell migration during humoral immune responses. Cell 99:351–354PubMedCrossRef

16.

Zlotnik A, Yoshie O (2000) Chemokines: a new classification system and their role in immunity. Immunity 12:121–127PubMedCrossRef

17.

Mackay C (2001) Chemokines: immunology’s high impact factors. Nat Immunol 2:95–101PubMedCrossRef

18.

Ma Q, Jones D, Springer T (1999) The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity 10(4):463–471PubMedCrossRef

19.

Schutyser E, Struyf S, Proost P, Opdenakker G, Laureys G, Verhasselt B, Peperstraete L, Van de Putte I, Saccani A, Allavena P, Mantovani A, Van Damme J (2002) 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 277(27):24584–24593PubMedCrossRef

20.

Negus RP, Stamp GW, Relf MG, Burke F, Malik ST, Bernasconi S, Allavena P, Sozzani S, Mantovani A, Balkwill FR (1995) The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. J Clin Invest 95(5):2391–2396PubMedCrossRef

21.

Freedman RS, Tomasovic B, Templin S, Atkinson EN, Kudelka A, Edwards CL, Platsoucas CD (1994) Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunotherapy. J Immunol Meth 167:145–160CrossRef

22.

Tukey JW (1951) Reminder sheets for “Discussion of paper on multiple comparisons by Henry Scheffe.” In: The collected works of John W Tukey VIII: multiple comparisons: 1948–1983ed. Chapman Hall, London pp 469–475

23.

Kim CH, Broxmeyer HE (1998) In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow environment. Blood 91(1):100–110PubMed

24.

Wang E (2005) RNA amplification for successful gene profiling analysis. J Trans Med 3:28CrossRef

25.

Wang E, Miller L, Ohnmacht GA, Liu E, Marincola FM (2000) High fidelity mRNA amplification for gene profiling. Nat Biotechnol 18:457–459PubMedCrossRef

26.

Imai T, Horiuchi A, Shiozawa T, Osada R, Kikuchi N, Ohira S, Oka K, Konishi I (2004) Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas. Hum Pathol 35(12):1469–1476PubMedCrossRef

27.

Scotton CJ, Milliken D, Wilson J, Raju S, Balkwill FR (2001) Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours. Br J Cancer 85(6):891–897PubMedCrossRef

28.

Freedman RS, Wang E, Voiculescu S, Patenia R, Bassett RL, Deavers M, Marincola FM, Yang P, Newman RA (2007) Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer. Clin Cancer Res 13(19):5736–5744PubMedCrossRef

29.

Giannone G, Dubin-Thaler BJ, Rossier O, Cai Y, Chaga O, Jiang G, Beaver W, Dobereiner HG, Freund Y, Borisy G, Sheetz MP (2007) Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 128(3):561–575PubMedCrossRef

30.

Schaub S, Meister JJ, Verkhovsky AB (2007) Analysis of actin filament network organization in lamellipodia by comparing experimental and simulated images. J Cell Sci 120(Pt 8):1491–1500PubMedCrossRef

31.

Sessa C, De Braud F, Perotti A, Bauer J, Curigliano G, Noberasco C, Zanaboni F, Gianni L, Marsoni S, Jimeno J, D’Incalci M, Dall’o E, Colombo N (2005) Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol 23(9):1867–1874PubMedCrossRef

32.

Nimmerjahn F, Ravetch JV (2005) Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science 310:1510–1512PubMedCrossRef

Title: Migration deficit in monocyte-macrophages in human ovarian cancer
Authors: Ralph S. Freedman
Qing Ma
Ena Wang
Stacie T. Gallardo
Ilyssa O. Gordon
Jeong Won Shin
Ping Jin
David Stroncek
Francesco M. Marincola
Publication date: 01-05-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 5/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0401-5

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Purpose

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