Thrombocytosis in patients with tumors producing colony-stimulating factor

Abstract

We investigated the cause of thrombocytosis in 14 patients with tumors producing colony-stimulating factor (CSF). Of the 14 patients, 10 had tumors producing granulocyte-CSF (G-CSF) and 4 had tumors producing granulocyte-macrophage--CSF (GM-CSF). Thrombocytosis of greater than 400 x 10(9)/L was noted in 8 of 10 patients with G-CSF-producing tumors and all 4 patients with GM-CSF-producing tumors. Median peak platelet counts were, respectively, 511 x 10(9)/L (range, 384 to 694 x 10(9)/L) and 579 x 10(9)/L (range, 526 to 910 x 10(9)/L) in patients with tumors producing G-CSF and GM-CSF. In most patients, thrombocytosis declined towards the terminal stage. High interleukin-1 (IL-1) and IL-6 levels were found in addition to CSFs in the plasma or culture supernatants of tumor cells obtained from most patients. In patients with GM-CSF- producing tumors, these specimens had megakaryocyte-CSF (Meg-CSF) activity, which was abolished by anti-GM-CSF antibody. These specimens also had megakaryocyte potentiating (Meg-Pot) activity attributable to both GM-CSF and IL-6. In patients with G-CSF-producing tumors, only Meg- Pot activity due to IL-6 was detected. These results indicate that the thrombocytosis in GM-CSF-producing tumors was caused by both the Meg- CSF activity of GM-CSF and the Meg-Pot activity of IL-6 plus GM-CSF, while that in G-CSF-producing tumors was due to the Meg-Pot activity of IL-6.

Modified combination of platelet count and neutrophil “to” lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer

“…Platelet‐derived transforming growth factor‐β acts on cancer cells to activate the Smad and nuclear factor‐kappa β pathways, thus promoting cancer metastasis . Additionally, cancer cells can produce tumor‐related humoral factors and cytokines, such as granulocyte colony‐stimulating factor and interleukin‐6, which stimulate thrombopoiesis …”

Involvement of Platelets in Cancers

“…13 Indeed, Suzuki et al reported 25 years ago that primary tumor cells could produce and secrete G-CSF and GM-CSF leading to the stimulation of megakaryopoieses and thrombopoesis. 27 Focusing on ovarian cancer, Stone et al reported that plasma levels of TPO and IL-6 were significantly higher in patients with thrombocytosis than those without. In addition, the authors demonstrated, in a mouse model, an increased hepatic TPO synthesis in response to tumor-derived IL-6 and showed a correlation with paraneoplastic thrombocytosis.…”

“…29,30 The elevation of TPO production promotes increased megakaryocyte growth differentiation and platelet production. [27][28][29][30][31] Tumor Cell-Induced Platelet Activation-Released Factors…”

“…90 Moreover, some authors have reported significant decrease of mortality due to colorectal and esophageal cancer with acetylsalicylic acid treatment. 89,91 Vanschoonbeek et al 22 Cedervall et al 23 Amirkhosravi et al 24 Simanek et al 11 Tumor cell Released factors involved in platelets activation P-selectin CD40 ligand Platelet factor 4 Thrombospondin-1 βthromboglobulin Platelet adenosine diphosphate G-CSF and GM-CSF Interleukin-1 and -6 thrombopoietin Caine et al 33 Huang et al 35 Peterson et al 37 Suh et al 38 Benedetti Panici et al 39 Henn et al 40 Haemmerle et al 44 Suzuki et al 27 Stone et al 28 Procoagulant proteins…”

Papel de C3G plaquetario en angiogénesis y metástasis tumoral

“…De hecho, en la mayoría de malignidades, el grado de trombocitosis en el paciente se encuentra inversamente correlacionado con su supervivencia, lo que le convierte en un marcador de mal pronóstico (Monreal et al, 1998;Symbas et al, 2000;Ikeda et al, 2002). Además, se conoce que los tumores pueden secretar citoquinas como IL-1, IL-6, GM-CSF y GCS-F, que estimulan la trombopoyesis y contribuyen al desarrollo de la trombocitosis (Suzuki et al, 1992;Estrov et al, 1995;Kaser et al, 2001).…”