Platelets actively sequester angiogenesis regulators.

Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non-tumor-bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (eg, albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm(3)) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (eg, platelet-derived growth factor, basic fibroblast growth factor) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts may have implications for the diagnosis and management of many angiogenesis-related diseases and provide a guide for antiangiogenic therapies.

Platelet interactions with calcium-phosphate-coated surfaces.

Many studies have shown that calcium-phosphate (CaP)-coated endosseous implants exhibit more peri-implant bone formation and bone contact at early healing times than uncoated implants. Since the rate of healing is influenced by blood/implant interactions and possibly the degree of blood platelet activation, the aim of this study was to determine whether the topography, microtopography, or the presence of calcium (Ca) and phosphate (PO(4)) ions in the implant surface plays a predominant role in platelet activation. We define the threshold between topography and microtopography as the limit of the scale range of platelets themselves; thus, a microtopographic surface is defined by one which exhibits features 3mum. With the help of four international collaborating laboratories, we prepared 11 titanium and CaP-modified titanium surfaces each with different (micro)topographies and interrogated these surfaces with both platelet adhesion (lactate dehydrogenase activity) and platelet activation (microparticle formation and P-selectin expression) assays. Our results show that: calcium (Ca)- and phosphate (PO(4))-containing surfaces of increasing surface microtopographical complexity exhibit increasing platelet activation; surfaces with similar surface microtopographies show similar levels of platelet activation regardless of the presence of Ca and PO(4) in the surface; and that surface microtopography is responsible for platelet activation rather than the presence of Ca and PO(4) in the surface.