Inhibition of Platelet-Derived Growth Factor Receptor Signaling Restricts the Growth of Human Breast Cancer in the Bone of Nude Mice
Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growt...
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Published in | Clinical cancer research Vol. 11; no. 1; pp. 306 - 314 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.01.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are
involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits
PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis.
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, PDGFRα, and PDGFRβ 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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.306.11.1 |