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Blood, 1 February 2008, Vol. 111, No. 3, pp. 974.

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INSIDE BLOOD

Platelets may serve up biomarkers

Bruce S. Sachais

UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE

Comment on Cervi et al, page 1201

In this issue of Blood, Cervi and colleagues used a proteomic technique known as mass spectroscopy to examine the platelet proteome of mice injected with a variety of tumor cells, compared with saline-injected controls. Among the proteins that differed in tumor-bearing mouse platelets, these investigators identified platelet factor 4 (PF4) as a biomarker of a variety of tumor types, including liposarcoma, osteosarcoma, and adenocarcinoma. A significant change in plasma PF4 was not detected.

These studies challenge us to look beyond traditional fluid sources of disease markers (plasma, urine, and cerebrospinal fluid). By examining platelets, Cervi et al were able to identify PF4 as a cancer-associated protein, even though PF4 levels do not change in the plasma. The lack of value of plasma PF4 as a biomarker in this study is not unexpected, as PF4 readily cleared from the plasma by binding to abundant gycosaminoglycans in the vasculature,1 highlighting the value of nontraditional biological samples to aid in the diagnosis of disease.

While Cervi et al used mass spectroscopy to identify and quantitate PF4 as a tumor biomarker, this technology is not widely available in clinical laboratories. The study demonstrates that increases in platelet PF4 can also be measured using the much simpler and more accessible method of ELISA. The use of ELISA in place of mass spectroscopy enhances our ability to validate the usefulness of platelet PF4 as a biomarker for early detection of cancer.

Although it is not a requirement, since biomarkers may simply have a disease association, biomarkers may have pathophysiological relevance to the disease that they identify. In this case, increases in platelet PF4 may be involved in tumor growth, as PF4 is known to regulate angiogenesis2,3 and may inhibit tumor growth.4 As such, PF4 in platelets represents not only a potentially useful cancer biomarker, but a potential target for early cancer therapy as well.


    Footnotes
 
DOI: 10.1182/blood-2007-10-118059

Footnotes

Conflict-of-interest disclosure: The author declares no competing financial interests. {blacksquare}

REFERENCES

  1. Rucinski B, Niewiarowski S, Strzyzewski M, Holt JC, Mayo KH. Human platelet factor 4 and its C-terminal peptides: heparin binding and clearance from the circulation. Thromb Haemost 1990; 63:493–498.[Medline] [Order article via Infotrieve]

  2. Maione TE, Gray GS, Petro J, et al. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 1990; 247:77–79.[Abstract/Free Full Text]

  3. Taylor S and Folkman J. Protamine is an inhibitor of angiogenesis. Nature 1982; 297:307–312.[CrossRef][Medline] [Order article via Infotrieve]

  4. Maione TE, Gray GS, Hunt AJ, Sharpe RJ. Inhibition of tumor growth in mice by an analogue of platelet factor 4 that lacks affinity for heparin and retains potent angiostatic activity. Cancer Res 1991; 51:2077–2083.[Abstract/Free Full Text]


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Related Article in Blood Online:

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
Blood 2008 111: 1201-1207. [Abstract] [Full Text] [PDF]




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