Submitted April 12, 2007
Accepted September 6, 2007
Platelet-associated PF-4 as a biomarker of early tumor growth
David Cervi, Tai-Tung Yip, Nandita Bhattacharya, Vladimir N Podust, Jon Peterson, Abdo Abou-Slaybi, George N. Naumov, Elise Bender, Nava Almog, Joseph E Italiano Jr, Judah Folkman, and Giannoula L. Klement*
Department of Surgery, Children's Hospital, Karp Family Research Laboratories, Boston, MA, United States
Diagnostics, Ciphergen Biosystems, Inc., Fremont, CA, United States
Research and Develovement, Ortho-Clinical Diagnostics, Rochester, NY, United States
Department of Hematology, Brigham and Women's Hospital, Boston, MA, United States
Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
* Corresponding author; email: giannoula.klement{at}childrens.harvard.edu.
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 SELDI-ToF MS proteomic comparison of platelets from normal and tumor-bearing mice. The differentially expressed protein band 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 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.
