Abstract | PURPOSE: EXPERIMENTAL DESIGN: Human breast cancer MDA-MB-435 cells were injected into the tibia of female nude mice. Two weeks later the mice were treated with p.o. and injected water (control), daily p.o. STI571, weekly injection of paclitaxel, or daily STI571, plus weekly paclitaxel, for up to 8 weeks. Growth of tumors in bones and osteolysis were monitored by digital radiography and tumors were collected for histochemical analysis. RESULTS: Mice treated with STI571 or STI571 plus paclitaxel had smaller bone tumors with less lytic bone destruction than did mice treated with water or paclitaxel alone. The results of treatment with paclitaxel plus STI571 did not differ from those with STI571 alone. Immunohistochemistry showed that PDGF-A, PDGF-B, PDGFRalpha, and PDGFRbeta were expressed in the bone tumors. STI571 treatment inhibited PDGFR phosphorylation in tumor cells and tumor-associated endothelial cells, coincident with increased apoptosis, reduced proliferation, and lower microvessel density in the tumors. CONCLUSIONS: Activated PDGFRs are expressed by endothelial and tumor cells in breast cancer tumors growing in the bone of nude mice. Interfering with PDGFR signaling may be an approach to control the progressive growth of breast cancer cells and thus reduce bone lysis.
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Authors | Dina Chelouche Lev, Sun Jin Kim, Amir Onn, Valerie Stone, Do-Hyun Nam, Sertac Yazici, Isaiah J Fidler, Janet E Price |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 1
Pg. 306-14
(Jan 01 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 15671560
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Benzamides
- Piperazines
- Platelet Endothelial Cell Adhesion Molecule-1
- Platelet-Derived Growth Factor
- Pyrimidines
- platelet-derived growth factor A
- Imatinib Mesylate
- Receptor, Platelet-Derived Growth Factor alpha
- Receptor, Platelet-Derived Growth Factor beta
- Receptors, Platelet-Derived Growth Factor
- Paclitaxel
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Benzamides
- Bone Neoplasms
(diagnostic imaging, drug therapy, metabolism, secondary)
- Bone Resorption
- Bone and Bones
(metabolism)
- Breast Neoplasms
(drug therapy, metabolism)
- Cell Line, Tumor
- Cell Proliferation
- Endothelial Cells
(metabolism)
- Female
- Humans
- Imatinib Mesylate
- Immunohistochemistry
- In Situ Nick-End Labeling
- Mice
- Mice, Nude
- Microcirculation
- Microscopy, Fluorescence
- Neoplasm Metastasis
- Neoplasm Transplantation
- Neovascularization, Pathologic
- Paclitaxel
(pharmacology)
- Phosphorylation
- Piperazines
(pharmacology)
- Platelet Endothelial Cell Adhesion Molecule-1
(biosynthesis)
- Platelet-Derived Growth Factor
(biosynthesis)
- Pyrimidines
(pharmacology)
- Radiography
- Receptor, Platelet-Derived Growth Factor alpha
(biosynthesis)
- Receptor, Platelet-Derived Growth Factor beta
(biosynthesis)
- Receptors, Platelet-Derived Growth Factor
(antagonists & inhibitors, metabolism)
- Signal Transduction
- Time Factors
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