title: Platelet-associated PF-4 as a biomarker of early tumor growth.
abstract: 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.
authors.affiliation: Children's Hospital Boston, Karp Family Research Laboratories, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cervi
authors.forename: Tai-Tung
authors.initials: TT
authors.lastname: Yip
authors.forename: Nandita
authors.initials: N
authors.lastname: Bhattacharya
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Podust
authors.forename: Jon
authors.initials: J
authors.lastname: Peterson
authors.forename: Abdo
authors.initials: A
authors.lastname: Abou-Slaybi
authors.forename: George N
authors.initials: GN
authors.lastname: Naumov
authors.forename: Elise
authors.initials: E
authors.lastname: Bender
authors.forename: Nava
authors.initials: N
authors.lastname: Almog
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
authors.forename: Judah
authors.initials: J
authors.lastname: Folkman
authors.forename: Giannoula L
authors.initials: GL
authors.lastname: Klement
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D006801:Humans; D007118:Immunoassay; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010978:Platelet Factor 4 / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D040901:Proteomics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D010978:Platelet Factor 4