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The Platelet Angiogenesis Proteome for Early Detection of Cancer
Author(s) -
Folkman Judah,
Cervi David,
Klement Giannoula,
Italiano Joe,
Yip TaiTong
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a414-c
Subject(s) - angiogenesis , platelet , biomarker , cancer , cancer research , endostatin , matrigel , medicine , proteome , pathology , chemistry , immunology , biology , bioinformatics , biochemistry
We report a novel function of platelets distinct from their hemostatic activity. We show 1 that platelets selectively take up angiogenesis regulatory proteins secreted by human tumors in mice, including VEGF, bFGF, PDGF, PF4, endostatin, angiostatin, and others, depending on tumor type. The platelet accumulation of these proteins significantly exceeds their concentration in platelets from animals not bearing a tumor. Nanomolar quantities of VEGF incorporated into a Matrigel pellet implanted subcutaneously in a mouse, or VEGF secreted by a microscopic subcutaneous tumor (0.5 – 1 mm 3 ), elevate VEGF levels in platelets, but not in plasma. After microscopic (< 1 mm 3 ),non‐angiogenic tumors switch to the angiogenic phenotype and grow to a sufficient tumor mass (~1 cm 3 ), angiogenesis regulatory proteins which previously increased only in platelets, begin to appear in the plasma. The “platelet angiogenesis proteome” provides a stable, sensitive and reliable biomarker for very early diagnosis of cancer, and for determining that tumors have switched to the angiogenic phenotype. If this biomarker can be validated in patients it may be used in conjunction with other biomarkers to diagnose the recurrence of cancer years before such a minute tumor burden would become symptomatic, or could be anatomically located by conventional methods. It could also be used to diagnose a new primary tumor, for example in women with the mutated breast cancer gene who have not yet developed a clinically detectable cancer.