Unfractionated and Low Molecular Weight Heparin Reduce Platelet Induced Epithelial-Mesenchymal Transition in Pancreatic and Prostate Cancer Cells

Abstract

The interaction with platelets is of crucial importance for tumor cells passing through hematogenous metastasis. Platelets protect cancer cells from immune surveillance and exhibit many other prometastatic effects. Notably, platelets can change the epithelial tumor phenotype, a process termed epithelial-mesenchymal transition (EMT), which confers stem cell-like properties onto tumor cells associated with an increased motility and drug resistance. The aim of the study is to investigate the impact of heparin on the platelet induced EMT program in pancreatic and prostate tumor cells. Platelet activation and interaction with cancer cells were determined by static adhesion assays. Applying ELISAs, the platelet release of EMT inducing mediators was quantified. EMT marker protein expression by tumor cells was explored by western blot and qPCR. Our data show that different tumor cell entities have different platelet binding capacities and also that a weak interaction is sufficient to change tumor cell phenotype. Additionally, unfractionated heparin (UFH) as well as low molecular weight heparin (LMWH) reduced tumor cell platelet interaction. Subsequently, attenuated platelet-derived mediator release resulted in reduced EMT marker protein and transcription factor expression by the cancer cells and decreased cell migration. These data suggest that heparin reduces platelet induced EMT program and prevents the formation of cancer cells with stem cell-like properties. This additional mechanism argues for the use of heparin in oncological applications.

λ-Carrageenan Oligosaccharides of Distinct Anti-Heparanase and Anticoagulant Activities Inhibit MDA-MB-231 Breast Cancer Cell Migration

“…As shown in Figure 5A, large number of control cells (treated with vehicle) passed through the pores towards the lower chambers in response to a 10% FBS (Fetal Bovine Serum) solution that was used as a chemoattractant. Treatment with native heparin led to a moderate 7.6% inhibition rate in accordance with previously published results [58,59,60]. Treatment with the λ-CO candidate at 100 μg·mL −1 significantly reduced the migration of MDA-MB-231 cells.…”

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

“…In order to survive, CTCs must overcome anoikis and immune surveillance once they detach from the primary tumor. One of the tools exploited by CTCs after entering the circulation is platelet activation; by inducing platelet aggregation, tumor cells are protected from immune surveillance, undergo cell arrest within the vasculature, and experience enhanced survival [91,92]. The CSCs phenotype of BC cells is associated with brain tropism in TNBC patients [93][94][95].…”

Challenges and Opportunities Associated With Platelets in Pancreatic Cancer

“…Ponert et al. ( 66 ) demonstrated that different cancer cells could easily bind to activated platelets in vitro , thereby accelerating the adhesion between platelets and tumor cells; this phenomenon was particularly prominent in PC cells. In another in vitro experiment, investigators observed that after many platelets aggregated by binding to PC PANC-1 cells, the migration, invasion and proliferation capacity of PANC-1 cells was significantly enhanced ( 24 , 67 ).…”