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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1201-1207.
Prepublished online as a Blood First Edition Paper on October 3, 2007; DOI 10.1182/blood-2007-04-084798.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Platelet-associated PF-4 as a biomarker of early tumor growth

David Cervi1, Tai-Tung Yip2, Nandita Bhattacharya1, Vladimir N. Podust2, Jon Peterson1,3, Abdo Abou-Slaybi1, George N. Naumov1, Elise Bender1, Nava Almog1, Joseph E. Italiano, Jr4, Judah Folkman1, and Giannoula L. Klement1,5

1 Children's Hospital Boston, Karp Family Research Laboratories, MA; 2 Ciphergen Biosystems, Fremont, CA; 3 Ortho-Clinical Diagnostics, Rochester, NY; 4 Brigham and Women's Hospital, and 5 Dana-Farber Cancer Institute, Boston, MA

Early tumor detection and intervention are important determinants of survival in patients with cancer. We have recently reported that the "platelet angiogenesis proteome" may be used to detect microscopic tumors in mice. We now present evidence that changes in platelet-associated platelet factor-4 (PF-4) detect malignant growth across a spectrum of human cancers in mice. A deregulated expression of an 8206-Da protein was observed by surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-ToF MS) proteomic comparison of platelets from normal and tumor-bearing mice. The differentially expressed protein was identified as PF-4 by tandem mass spectrometry and ProteinChip immunoassay using anti–PF-4 antibody. The platelet-associated PF-4 appeared to be up-regulated in early growth of human liposarcoma, mammary adenocarcinoma, and osteosarcoma. A 120-day follow-up study of liposarcoma revealed a sustained 2-fold or higher increase of platelet-associated PF-4 at 19, 30, and 120 days. In contrast, only an insignificant change of PF-4 was observed in the plasma of mice bearing the different human tumor xenografts, and throughout the 120 days of the liposarcoma study. We conclude that platelet-associated PF-4, but not its plasma counterpart, may represent a potential biomarker of early tumor presence.


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Related Article in Blood Online:

Platelets may serve up biomarkers
Bruce S. Sachais
Blood 2008 111: 974. [Full Text] [PDF]





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