Summary
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.
Similar content being viewed by others
References
B Homey A Muller A Zlotnik (2002) ArticleTitleChemokines: Agents for the immunotherapy of cancer Nat Rev Immunol 2 175–184
A Muller B Homey H Soto N Ge D Catron ME Buchanan T McClanahan E Murphy W Yuan SN Wagner JL Barrera A Mohar E Verastegui A Zlotnik (2001) ArticleTitleInvolvement of chemokine receptors in breast cancer metastasis Nature 410 50–56 Occurrence Handle1:CAS:528:DC%2BD3MXhvVSgu74%3D Occurrence Handle11242036
M Brault RA Kurt (2003) ArticleTitleChemokines and anti-tumor immunity: walking the tightrope Int Rev Immunol 22 199–228
AP Adler CA Lemken NS Katchen RA Kurt (2003) ArticleTitleA dual role for tumor-derived chemokine RANTES (CCL5) Immunol Lett 90 187–194
L Peng S Shu JC Krauss (1997) ArticleTitleMonocyte chemoattractant protein inhibits the generation of tumor-reactive T cells Cancer Res 57 4849–4854
D Schadendorf A Moller B Algermissen M Worm M Sticherling BM Czarnetzki (1993) ArticleTitleIL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor J Immunol 151 2667–2675
JM Wang X Deng W Gong S Su (1998) ArticleTitleChemokines and their role in tumor growth and metastasis J Immunol Methods 220 1–17
Y Niwa H Akamatsu H Niwa H Sumi Y Ozamki A Abe (2001) ArticleTitleCorrelation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer Clin Cancer Res 7 285–289
G Luboshits S Shina O Kaplan S Engelberg D Nass B Lifshitz-Mercer S Chaitchik I Keydar A Ben-Baruch (1999) ArticleTitleElevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma Cancer Res 59 4681–4687
TJ Schall J Jongstra BJ Dyer J Jorgensen C Clayberger MM Davis AM Krensky (1988) ArticleTitleA human T cell-specific molecule is a member of a new gene family J Immunol 141 1018–1025
AE John AA Berlin NW Lukacs (2003) ArticleTitleRespiratory syncytial virus-induced CCL5/RANTES contributes to exacerbation of allergic airway inflammation Eur J Immunol 33 1677–1685
RA Kurt A Baher KP Wisner S Tackitt WJ Urba (2001) ArticleTitleChemokine receptor desensitization in tumor-bearing mice Cell Immunol 207 81–88
CJ Aslakson FR Miller (1992) ArticleTitleSelective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor Cancer Res 52 1399–1405
E Azenshtein G Luboshits S Shina E Neumark D Shahbazian M Weil N Wigler I Keydar A Ben-Baruch (2002) ArticleTitleThe CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity Cancer Res 62 1093–1102 Occurrence Handle1:CAS:528:DC%2BD38XitVSmsbc%3D Occurrence Handle11861388
J Hua RJ Muschel (1996) ArticleTitleInhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model Cancer Res 56 5279–5284
S Yagel AH Warner HN Nellans PK Lala C Waghorne DT Denhardt (1989) ArticleTitleSuppression of cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cells Cancer Res 49 3553–3557
AM Tester M Waltham SJ Oh SN Bae NM Bills EC Walker FG Kern WG Stetler-Stevenson ME Lippman EW Thompson (2004) ArticleTitlePro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice Cancer Res 15 652–658
G Ghilardi ML Biondi M Caputo S Leviti M DeMonti E Guagnellini R Scorza (2002) ArticleTitleA single nucleotide polymorphism in the matrix metalloproteinase-3 promoter enhances breast cancer susceptibility Clin Cancer Res 8 3820–3823
T Sreenath LM Matrisian W Stetler-Stevenson S Gattoni-Celli RO Pozzatti (1992) ArticleTitleExpression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential Cancer Res 52 4942–4947
XS Peunte AM Pendas E Llano G Velasco C Lopez-Otin (1996) ArticleTitleMolecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma Cancer Res 56 944–949
R Colella SF Casey (2003) ArticleTitleDecreased activity of cathepsins L + B and decreased invasive ability of PC3 prostate cancer cells Biotech Histochem 75 101–108
N Levicar RA Dewey E Daley TE Bates D Davies J Kos GJ Pilkington TT Lah (2003) ArticleTitleSelective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis Cancer Gene Ther 10 141–151
C Thomssen M Schmitt L Goretzki P Oppelt L Pache P Dettmar F Janicke H Graeff (1995) ArticleTitlePrognostic value of the cysteine proteases cathepsins B and cathepsin L in human breast cancer Clin Cancer Res 1 741–746
M Locati U Deuschle ML Massardi FO Martinez M Sironi S Sozzani T Bartfai A Mantovani (2002) ArticleTitleAnalysis of the gene expression profile activated by the CC chemokine ligand 5/RANTES and by lipopolysaccharide in human monocytes J Immunol 168 3557–3562
V Sriraman JS Richards (2004) ArticleTitleCathepsin L gene expression and promoter activation in rodent granulosa cells Endocrinology 145 582–591
H Nagase JF Woessner (1999) ArticleTitleMatrix metalloproteinases J Biol Chem 274 21491–21494
WG Stetler-Stevenson (2001) ArticleTitleThe role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis Surg Oncol Clin N Am 10 383–392
GH Yuan K Masuko-Hongo M Sakata J Tsuruha H Onuma H Nakamura H Aoki T Kato K Nishioka (2001) ArticleTitleThe role of C–C chemokines and their receptors in osteoarthritis Arthritis Rheum 44 1056–1070 Occurrence Handle1:CAS:528:DC%2BD38XptlQ%3D Occurrence Handle11352237
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stormes, K.A., Lemken, C.A., Lepre, J.V. et al. Inhibition of metastasis by inhibition of tumor-derived CCL5. Breast Cancer Res Treat 89, 209–212 (2005). https://doi.org/10.1007/s10549-004-5328-3
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10549-004-5328-3