Breast Cancer Research and Treatment

, Volume 89, Issue 2, pp 209–212 | Cite as

Inhibition of metastasis by inhibition of tumor-derived CCL5

  • Kerry A. Stormes
  • Charles A. Lemken
  • James V. Lepre
  • Michelle N. Marinucci
  • Robert A. Kurt
Brief communication


To determine whether tumor-derived CCL5 contributes to the metastatic potential of murine mammary carcinoma, we used the 4T1 tumor which spontaneously metastasizes and constitutively produces CCL5. Mice bearing 4T1 that expressed less CCL5 had significantly fewer lung and liver metastasis. The decrease in tumor-derived CCL5 also correlated with decreased cathepsin L, MMP-2, MMP-3, MMP-10 and MMP-17 gene expression. Thus, inhibition of tumor-derived CCL5 can impact the metastatic capability of 4T1 and may do so by modulating protease expression.

Key words

breast cancer CCL5 metastasis RANTES 4T1 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Homey, B, Muller, A, Zlotnik, A 2002Chemokines: Agents for the immunotherapy of cancerNat Rev Immunol2175184Google Scholar
  2. Muller, A, Homey, B, Soto, H, Ge, N, Catron, D, Buchanan, ME, McClanahan, T, Murphy, E, Yuan, W, Wagner, SN, Barrera, JL, Mohar, A, Verastegui, E, Zlotnik, A 2001Involvement of chemokine receptors in breast cancer metastasisNature4105056PubMedGoogle Scholar
  3. Brault, M, Kurt, RA 2003Chemokines and anti-tumor immunity: walking the tightropeInt Rev Immunol22199228Google Scholar
  4. Adler, AP, Lemken, CA, Katchen, NS, Kurt, RA 2003A dual role for tumor-derived chemokine RANTES (CCL5)Immunol Lett90187194Google Scholar
  5. Peng, L, Shu, S, Krauss, JC 1997Monocyte chemoattractant protein inhibits the generation of tumor-reactive T cellsCancer Res5748494854Google Scholar
  6. Schadendorf, D, Moller, A, Algermissen, B, Worm, M, Sticherling, M, Czarnetzki, BM 1993IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factorJ Immunol15126672675Google Scholar
  7. Wang, JM, Deng, X, Gong, W, Su, S 1998Chemokines and their role in tumor growth and metastasisJ Immunol Methods220117Google Scholar
  8. Niwa, Y, Akamatsu, H, Niwa, H, Sumi, H, Ozamki, Y, Abe, A 2001Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancerClin Cancer Res7285289Google Scholar
  9. Luboshits, G, Shina, S, Kaplan, O, Engelberg, S, Nass, D, Lifshitz-Mercer, B, Chaitchik, S, Keydar, I, Ben-Baruch, A 1999Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinomaCancer Res5946814687Google Scholar
  10. Schall, TJ, Jongstra, J, Dyer, BJ, Jorgensen, J, Clayberger, C, Davis, MM, Krensky, AM 1988A human T cell-specific molecule is a member of a new gene familyJ Immunol14110181025Google Scholar
  11. John, AE, Berlin, AA, Lukacs, NW 2003Respiratory syncytial virus-induced CCL5/RANTES contributes to exacerbation of allergic airway inflammationEur J Immunol3316771685Google Scholar
  12. Kurt, RA, Baher, A, Wisner, KP, Tackitt, S, Urba, WJ 2001Chemokine receptor desensitization in tumor-bearing miceCell Immunol2078188Google Scholar
  13. Aslakson, CJ, Miller, FR 1992Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumorCancer Res5213991405Google Scholar
  14. Azenshtein, E, Luboshits, G, Shina, S, Neumark, E, Shahbazian, D, Weil, M, Wigler, N, Keydar, I, Ben-Baruch, A 2002The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activityCancer Res6210931102PubMedGoogle Scholar
  15. Hua, J, Muschel, RJ 1996Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma modelCancer Res5652795284Google Scholar
  16. Yagel, S, Warner, AH, Nellans, HN, Lala, PK, Waghorne, C, Denhardt, DT 1989Suppression of cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cellsCancer Res4935533557Google Scholar
  17. Tester, AM, Waltham, M, Oh, SJ, Bae, SN, Bills, NM, Walker, EC, Kern, FG, Stetler-Stevenson, WG, Lippman, ME, Thompson, EW 2004Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude miceCancer Res15652658Google Scholar
  18. Ghilardi, G, Biondi, ML, Caputo, M, Leviti, S, DeMonti, M, Guagnellini, E, Scorza, R 2002A single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibilityClin Cancer Res838203823Google Scholar
  19. Sreenath, T, Matrisian, LM, Stetler-Stevenson, W, Gattoni-Celli, S, Pozzatti, RO 1992Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potentialCancer Res5249424947Google Scholar
  20. Peunte, XS, Pendas, AM, Llano, E, Velasco, G, Lopez-Otin, C 1996Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinomaCancer Res56944949Google Scholar
  21. Colella, R, Casey, SF 2003Decreased activity of cathepsins L + B and decreased invasive ability of PC3 prostate cancer cellsBiotech Histochem75101108Google Scholar
  22. Levicar, N, Dewey, RA, Daley, E, Bates, TE, Davies, D, Kos, J, Pilkington, GJ, Lah, TT 2003Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosisCancer Gene Ther10141151Google Scholar
  23. Thomssen, C, Schmitt, M, Goretzki, L, Oppelt, P, Pache, L, Dettmar, P, Janicke, F, Graeff, H 1995Prognostic value of the cysteine proteases cathepsins B and cathepsin L in human breast cancerClin Cancer Res1741746Google Scholar
  24. Locati, M, Deuschle, U, Massardi, ML, Martinez, FO, Sironi, M, Sozzani, S, Bartfai, T, Mantovani, A 2002Analysis of the gene expression profile activated by the CC chemokine ligand 5/RANTES and by lipopolysaccharide in human monocytesJ Immunol16835573562Google Scholar
  25. Sriraman, V, Richards, JS 2004Cathepsin L gene expression and promoter activation in rodent granulosa cellsEndocrinology145582591Google Scholar
  26. Nagase, H, Woessner, JF 1999Matrix metalloproteinasesJ Biol Chem2742149121494Google Scholar
  27. Stetler-Stevenson, WG 2001The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesisSurg Oncol Clin N Am10383392Google Scholar
  28. Yuan, GH, Masuko-Hongo, K, Sakata, M, Tsuruha, J, Onuma, H, Nakamura, H, Aoki, H, Kato, T, Nishioka, K 2001The role of C–C chemokines and their receptors in osteoarthritisArthritis Rheum4410561070PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Kerry A. Stormes
    • 1
  • Charles A. Lemken
    • 1
  • James V. Lepre
    • 1
  • Michelle N. Marinucci
    • 1
  • Robert A. Kurt
    • 1
  1. 1.Department of BiologyLafayette CollegeEastonUSA

Personalised recommendations