Platelet releasate promotes breast cancer growth and angiogenesis via VEGF–integrin cooperative signalling

Abstract

Background:Selective platelet release of pro- or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth.Methods:Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors).Results:The PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary-like tube formation of endothelial cells that was further enhanced by pro-angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1α, receptor blockade abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB-231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4-PR, and seemed to achieve the exaggeration by promoting more profound tumour angiogenesis.Conclusions:Platelet releasate increases breast cancer cell proliferation through VEGF–integrin cooperative signalling. Pro-angiogenic factor-rich platelet releasate enhances cancer cell-induced angiogenesis more markedly, and thus exaggerates tumour growth in vivo.

<p>Pretreatment Systemic Inflammation Response Index in Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy as a Useful Prognostic Indicator</p>

“…33,34 Platelets are an indicator of tumor activity and angiogenesis, and are associated with tumor growth, invasion, and metastasis by releasing VEGF-integrin cooperative signaling. 35,36 Moreover, lymphocytes are an important component of anticancer immunity and immune surveillance and are associated to prevent the tumor growth and progression. 37,38 Some studies have shown that inflammatory markers and immune-based prognostic indexes were used to evaluate the prognosis of breast cancer, such as NLR, d-NLR, MLR/LMR, and PLR.…”

Platelet biology in regenerative medicine of skeletal muscle

“…Several studies have focused on releasate, which is a refined, centrifuged and purified sample of growth factors released from aggregated platelets when the supernatant is collected, and cellular debris removed . Soluble bioactive molecules in the releasate secreted by the α‐granules of platelets are known to enhance matrix synthesis (eg, TGF‐β), upregulate chemo‐attraction and proliferation in several cell types (eg, PDGF, VEGF, IGF‐I and IGF‐II, EGF and ECGF) (Figure ) and angiogenesis (eg, VEGF, FGF and ECGF) .…”

Dopamine Delivery via pH‐Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs

“…Based on active metabolism of tumor cells on continuous desire to oxygen and nutrient, they release and produce high amounts of proangiogenic factors that promote nourishing the vessel growth . These are some main positive regulator of angiogenesis, such as vascular endothelial growth factor (VEGF), fibroblast growth factor‐2 (FGF‐2), interleukin‐8 (IL‐8), placental growth factor (PlGF), transforming growth factor beta (TGFbeta), platelet derived growth factor (PDGF), angiopoietins (Angs), etc …”