Author's Accepted Manuscript

Guest Editorial: Platelets and Cancer

Brian I. Carr MD, FRCP, PhD.

PII: S0093-7754(14)00116-XDOI: http://dx.doi.org/10.1053/j.seminoncol.2014.04.011Reference: YSONC51709

To appear in: Semin Oncol

Cite this article as: Brian I. Carr MD, FRCP, PhD., Guest Editorial: Platelets andCancer, Semin Oncol, http://dx.doi.org/10.1053/j.seminoncol.2014.04.011

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Guest Editorial: Platelets and Cancer

Abstract

Platelets have a well-studied role in coagulation and in thromboembolism. The latter was recognized to

be a feature of occult cancer over 100 years ago. It has been increasingly appreciated, that as a

component of the tumor microenvironment, platelets also have important functions in the mechanisms

involved in carcinogenesis, tumor growth, tumor angiogenesis, tumor-related host organ inflammation

and immune responses, tumor metastasis and in the modulation of tumor therapy. Therapeutic

alteration of platelet numbers and function has increasingly gained attention for cancer prevention,

survival prolongation and possibly for therapy. The idea that systemic response to the presence of

cancer, including the platelet lymphocyte ratio (PLR) is an independent prognostic factor in many

tumor types, has recently gained support. Platelets are thus seen as predictors of cancer prognosis,

mediators of cancer biology and the subject of therapeutic intervention.

Article

Venous thromboembolism was first noted to be associated with cancer by Trousseau (1). It tends to be

recurrent, migratory, involves multiple body sites and can be resistant to anticoagulation (2, 3). This

cancer-associated thromboembolism was also found to be associated with thrombocytosis (4, 5).

Platelets have come to be viewed, both as a systemic reaction to the presence of cancer (6-9) as well

integral mediators of cancer biology (10-13). The actions of platelets on tumors may be direct (14, 15)

or as part of the tumor microenvironment (16, 17), although these are not mutually exclusive.

Thrombocytosis can occur in association with many cancers, including those of ovary (18), GI tract

(19) and liver (20, 21). Platelets typically derive from pro-platelet protrusions of megakaryocyte

cytoplasm, by processes that depend on cell-cell interactions in the bone marrow microenvironment

(22), as well as cytokines such as thrombopoietin, which is produced in the liver and by many tumors.

Recent clinical evidence points to a feed-back loop involving interleukin-6, thrombopoietin and

thrombocytosis, as described for ovarian cancer patients (18).

Several mechanisms have been suggested for the involvement of platelets in cancer development,

including their actions as a shield on tumor cells from immune attack, their role in tumor

vasculogenesis/vascularity, and their contribution to tumor growth via direct interactions and through

secreted inflammatory cytokines (23) and multiple tumor growth factors (24) carried in their granules

or in growth factor-rich platelet microvesicles that are shed from the surfaces of activated platelets.

These factors include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF),

serotonin, platelet-derived growth factors (PDGF), insulin-like growth factor-1 (IGF-1), epidermal

growth factor (EGF), transforming growth factor beta (TGFβ) and interleukins.

Many studies have addressed the involvement of platelets in tumor cell tethering, spreading, migration

and invasion (25-29), processes that are associated with metastasis, and platelet depletion has been

shown to diminish metastasis, apparently without altering the growth of the primary tumor (30).

Furthermore, platelets have also been shown to modify the response of tumors to cancer chemotherapy

(31, 32).

Furthermore, epidemiologic studies on the use of anti-platelet agents such as aspirin, have provided

recent evidence for an effect both in cancer prevention, as well as in improvement in survival of

patients with a diagnosis of cancer (33,34). The first four articles in this special Platelets and Cancer

issue, deal with the effects of cancer on platelets and the treatments for cancer-associated

thromboembolism. The subsequent ten articles, conversely, deal with the effects of platelets in

modulating cancer biology and possible therapeutic interventions to alter these effects.

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Brian I. Carr MD, FRCP, PhD. April 2014

Correspondence: Brian I. Carr MD, FRCP, PhD

IRCCS’ de Bellis’, via Turi 27, 70013 Castellana Grotte (BA), Italy

Tel. 39 080 4994603; Fax. 39 080 4994313

E-mail: brianicarr@hotmail.com