Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70 depletion

Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly expressed in human tumors. Here we demonstrate that locoregional application of adenovirus expressing antisense Hsp70 cDNA (Ad.asHsp70) eradicates orthotopic xenografts of glioblastoma and breast carcinoma, as well as s.c. xe...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-12, Vol.62 (24), p.7139-7142
Main Authors: NYLANDSTED, Jesper, WICK, Wolfgang, HIRT, Ulrich A, BRAND, Karsten, ROHDE, Mikkel, LEIST, Marcel, WELLER, Michael, JÄÄTTELÄ, Marja
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Apoptosis - physiology
Applied cell therapy and gene therapy
Biological and medical sciences
Brain Neoplasms - genetics
Brain Neoplasms - immunology
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Breast Neoplasms - genetics
Breast Neoplasms - immunology
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Colonic Neoplasms - genetics
Colonic Neoplasms - immunology
Colonic Neoplasms - pathology
Colonic Neoplasms - therapy
DNA, Antisense - genetics
DNA, Antisense - pharmacology
Female
Glioblastoma - genetics
Glioblastoma - immunology
Glioblastoma - pathology
Glioblastoma - therapy
HSP70 Heat-Shock Proteins - deficiency
HSP70 Heat-Shock Proteins - genetics
Humans
Macrophage Activation - immunology
Macrophages - immunology
Medical sciences
Mice
Mice, Inbred BALB C
Mice, SCID
Phagocytosis
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Summary:Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly expressed in human tumors. Here we demonstrate that locoregional application of adenovirus expressing antisense Hsp70 cDNA (Ad.asHsp70) eradicates orthotopic xenografts of glioblastoma and breast carcinoma, as well as s.c. xenografts of colon carcinoma in immunodeficient mice. Ad.asHsp70-treated tumors showed massive apoptosis-like cell death and recruitment of macrophages. Human monocyte-derived macrophages effectively removed the corpses of Ad.asHsp70-treated tumor cells in vitro. Interestingly, both tumor cell death and phagocytosis were caspase-independent. Thus, Hsp70 appears as a promising target for the treatment of cancers resistant to classic caspase-mediated apoptosis.
ISSN:0008-5472
1538-7445