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Tumor
Growth: A Putative Role for Platelets?
Verheul
HM, Pinedo HM
Department
of Medical Oncology, Free University Hospital, 1081 HV Amsterdam, The
Netherlands
Tumors
do not grow without inducing a new vessel formation.
The postulation of Dr. Folkman in 1971-that tumor growth is
angiogenesis-dependent- has been widely accepted, more than two decades
later.
The question now becomes, "Is it possible to treat cancer by attacking its
blood supply?"
Many pharmaceutical companies directed their research to antiangiogenic therapy
in the past years.
Despite increasing knowledge of tumor-induced angiogenesis, the mechanism as to
how antiangiogenic agents inhibit new vessel formation remains unknown.
Even the mechanisms of two of the most potent preclinical antiangiogenic drugs,
angiostatin and endostatin, are still unknown. Many factors are involved in new
vessel formation and experimental models are not sophisticated enough to take
into account all factors that play a role in spontaneously occurring
tumors.
Translational research from the clinic to the laboratory is warranted for the
discovery of new potent antiangiogenic agents.
Our translational angiogenesis research started two years ago, when we
hypothesized that circulating concentrations of vascular endothelial growth
factor (VEGF), an important angiogenic factor, if initially elevated, would
decrease during therapy in cancer patients.
Until then, several investigators tried to correlate serum concentrations of
VEGF with the prognosis of cancer patients. Fascinatingly, we found a specific
pattern of VEGF concentrations that correlated exactly with the platelet counts
of these patients during therapy.
No relationship with tumor burden was detected, indicating that circulating
levels of VEGF are not influenced by tumor cells, but are mainly dependent on
platelet contents.
In addition, it was shown by others that thrombin activation of platelets causes
VEGF release.
What then is the role of circulating VEGF carried by platelets?
VEGF has been shown to induce permeability, has mitogenic and chemotactic
activity on endothelial cells, and also has procoagulatory activity.
Platelets play a critical role in wound healing and, if they are activated, they
release upon activation, in addition to VEGF, other growth factors that are
involved in angiogenesis (e.g., platelet-derived endothelial cell growth factor,
thrombospondin, and platelet factor 4).
On the other hand, in the clinic it was found that platelet counts have
prognostic significance for cancer patients and that coagulation abnormalities
are regularly found in cancer patients.
In preclinical studies the tumor-platelet interactions have been studied
extensively and a relationship between metastasis formation and platelet-tumor
interaction has been reported.
We are currently investigating whether a specific tumor endothelium-platelet
interaction can contribute to tumor-induced angiogenesis.
Although these translational studies have no direct impact on clinical cancer
therapy, oncologists should be aware of a potential role for platelets in cancer
growth.
For example, bone marrow-supportive agents, currently used in high-dose
chemotherapy, contribute to platelet production and thereby may influence
response to therapy.
At this time we investigate in our hospital the pretreatment platelet counts in
cancer patients, and we are studying how bone marrow-supportive agents during
chemotherapy affect these counts in relation to the response to therapy.
We would be pleased to learn of your observations.
PMID:
10388096 [PubMed - as supplied by publisher]
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