Journal article
Platelet and osteoclast β3 integrins are critical for bone metastasis
Proceedings of the National Academy of Sciences - PNAS, Vol.100(24), pp.14205-14210
11/25/2003
DOI: 10.1073/pnas.2234372100
PMCID: PMC283570
PMID: 14612570
Abstract
Mice with a targeted deletion of β3 integrin were used to examine the process by which tumor cells metastasize and destroy bone. Injection of B16 melanoma cells into the left cardiac ventricle resulted in osteolytic bone metastasis in 74% of β3+/+ mice by 14 days. In contrast, only 4% of β3–/– mice developed bone lesions. Direct intratibial inoculation of tumor resulted in marrow replacement by tumor in β3–/– mice, but no associated trabecular bone resorption as seen inβ3+/+ mice. Bone marrow transplantation studies showed that susceptibility to bone metastasis was conferred by a bone marrow-derived cell. To dissect the roles of osteoclast and platelet β3 integrins in this model of bone metastasis, osteoclast-defective src–/– mice were used. Src-null mice were protected from tumor-associated bone destruction but were not protected from tumor cell metastasis to bone. In contrast, a highly specific platelet aggregation inhibitor of activated αIIbβ3 prevented B16 metastases. These data demonstrate a critical role for platelet αIIbβ3 in tumor entry into bone and suggest a mechanism by which antiplatelet therapy may be beneficial in preventing the metastasis of solid tumors.
Details
- Title: Subtitle
- Platelet and osteoclast β3 integrins are critical for bone metastasis
- Creators
- Suzanne J Bakewell - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Patrick Nestor - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Srinivasa Prasad - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Michael H Tomasson - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Nikki Dowland - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Mukund Mehrotra - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Robert Scarborough - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205James Kanter - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Keith Abe - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205David Phillips - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205Katherine N Weilbaecher - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 505, Little Rock, AR 72205
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.100(24), pp.14205-14210
- DOI
- 10.1073/pnas.2234372100
- PMID
- 14612570
- PMCID
- PMC283570
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 11/25/2003
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094340502771
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