BACKGROUND AIMS: Un-engineered human and rat umbilical cord matrix stem cells (UCMSCs) attenuate growth of several types of tumors in mice and rats. However, the mechanism by which UCMSCs attenuate tumor growth has not been studied rigorously. METHODS: The possible mechanisms of tumor growth attenuation by rat UCMSCs were studied using orthotopic Mat B III rat mammary tumor grafts in female F344 rats. Tumor-infiltrating leukocytes were identified and quantified by immunohistochemistry analysis. Potential cytokines involved in lymphocyte infiltration in the tumors were determined by microarray and Western blot analysis. The Boyden chamber migration assay was performed for the functional analysis of identified cytokines. RESULTS: Rat UCMSCs markedly attenuated tumor growth; this attenuation was accompanied by considerable lymphocyte infiltration. Immunohistochemistry analysis revealed that most infiltrating lymphocytes in the rat UCMSC-treated tumors were CD3(+) T cells. In addition, treatment with rat UCMSCs significantly increased infiltration of CD8(+) and CD4(+) T cells and natural killer (NK) cells throughout tumor tissue. CD68(+) monocytes/macrophages and Foxp3(+) regulatory T cells were scarcely observed, only in the tumors of the phosphate-buffered saline control group. Microarray analysis of rat UCMSCs demonstrated that monocyte chemotactic protein-1 is involved in rat UCMSC-induced lymphocyte infiltration in the tumor tissues. CONCLUSIONS: These results suggest that naïve rat UCMSCs attenuated mammary tumor growth at least in part by enhancing host anti-tumor immune responses. Naïve UCMSCs can be used as powerful therapeutic cells for breast cancer treatment, and monocyte chemotactic protein-1 may be a key molecule to enhance the effect of UCMSCs at the tumor site.
BACKGROUND AIMS: Un-engineered human and rat umbilical cord matrix stem cells (UCMSCs) attenuate growth of several types of tumors in mice and rats. However, the mechanism by which UCMSCs attenuate tumor growth has not been studied rigorously. METHODS: The possible mechanisms of tumor growth attenuation by rat UCMSCs were studied using orthotopic Mat B IIIrat mammary tumor grafts in female F344 rats. Tumor-infiltrating leukocytes were identified and quantified by immunohistochemistry analysis. Potential cytokines involved in lymphocyte infiltration in the tumors were determined by microarray and Western blot analysis. The Boyden chamber migration assay was performed for the functional analysis of identified cytokines. RESULTS:Rat UCMSCs markedly attenuated tumor growth; this attenuation was accompanied by considerable lymphocyte infiltration. Immunohistochemistry analysis revealed that most infiltrating lymphocytes in the rat UCMSC-treated tumors were CD3(+) T cells. In addition, treatment with rat UCMSCs significantly increased infiltration of CD8(+) and CD4(+) T cells and natural killer (NK) cells throughout tumor tissue. CD68(+) monocytes/macrophages and Foxp3(+) regulatory T cells were scarcely observed, only in the tumors of the phosphate-buffered saline control group. Microarray analysis of rat UCMSCs demonstrated that monocyte chemotactic protein-1 is involved in rat UCMSC-induced lymphocyte infiltration in the tumor tissues. CONCLUSIONS: These results suggest that naïve rat UCMSCs attenuated mammary tumor growth at least in part by enhancing host anti-tumor immune responses. Naïve UCMSCs can be used as powerful therapeutic cells for breast cancer treatment, and monocyte chemotactic protein-1 may be a key molecule to enhance the effect of UCMSCs at the tumor site.
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Authors: X Dong-Le Bourhis; Y Berthois; G Millot; A Degeorges; M Sylvi; P M Martin; F Calvo Journal: Int J Cancer Date: 1997-03-28 Impact factor: 7.396
Authors: K E van Roozendaal; J G Klijn; B van Ooijen; C Claassen; A M Eggermont; S C Henzen-Logmans; J A Foekens Journal: Int J Cancer Date: 1996-01-03 Impact factor: 7.396
Authors: E Ryschich; O Cebotari; O V Fabian; F Autschbach; J Kleeff; H Friess; A Bierhaus; M W Büchler; J Schmidt Journal: Tissue Antigens Date: 2004-12
Authors: Sandeep S Dave; George Wright; Bruce Tan; Andreas Rosenwald; Randy D Gascoyne; Wing C Chan; Richard I Fisher; Rita M Braziel; Lisa M Rimsza; Thomas M Grogan; Thomas P Miller; Michael LeBlanc; Timothy C Greiner; Dennis D Weisenburger; James C Lynch; Julie Vose; James O Armitage; Erlend B Smeland; Stein Kvaloy; Harald Holte; Jan Delabie; Joseph M Connors; Peter M Lansdorp; Qin Ouyang; T Andrew Lister; Andrew J Davies; Andrew J Norton; H Konrad Muller-Hermelink; German Ott; Elias Campo; Emilio Montserrat; Wyndham H Wilson; Elaine S Jaffe; Richard Simon; Liming Yang; John Powell; Hong Zhao; Neta Goldschmidt; Michael Chiorazzi; Louis M Staudt Journal: N Engl J Med Date: 2004-11-18 Impact factor: 91.245
Authors: Andrea Sadlonova; Zdenek Novak; Martin R Johnson; Damon B Bowe; Sandra R Gault; Grier P Page; Jaideep V Thottassery; Danny R Welch; Andra R Frost Journal: Breast Cancer Res Date: 2004-11-08 Impact factor: 6.466