PB1445 - Platelet-tumor cell interaction is mediated by fibrin mesh, which opens a possibility for reduction of metastasis by late-stage anticoagulation

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Anna Boldova, PhD

PhD student
Center for Theoretical Problems of Physicochemical Pharmacology
Moscow, Moskva, Russia

Co-Author(s)

AK

Anna Korneichuk

Researcher
Center for Theoretical Problems of Physicochemical Pharmacology
Moscow, Moskva, Russia
EB

Ekaterina Blinova

Professor
Sechenov University
Moscow, Moskva, Russia
IT

Ivan Tesakov

Researcher
Dmitry Rogachev National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology
Moscow, Moskva, Russia
KM

Kristina Mazova

Researcher
Sechenov University
Moscow, Moskva, Russia
VP

Viktoria Pakina

Researcher
Sechenov University
Moscow, Moskva, Russia
DB

Dmitrii Blinov

Professor
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, Moskva, Russia
Ekaterina V. Shamova, PhD

Head of Laboratory of Medical Biophysics
Institute of biophysics and cell engineering NAS of Belarus, Minsk, Belarus
Minsk, Minskaya Voblasts', Belarus
AS

Anastasia N. Sveshnikova

Head of Laboratory
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Moscow, Moskva, Russia

Background: Metastasis is the main complication of solid tumors, and is known to depend on the interaction of tumor cells with platelets in the blood stream.

Aims: Investigation of platelet interaction with tumor cells.

Methods: Light transmission aggregometry and confocal microscopy were used for characterization of human platelets' interaction with tumor cells: breast cancer (MCF-7), cervical cancer (SiHa) and neuroblastoma (SH-SY5Y). A murine model of Lewis carcinoma (15 C57/B6 female mice) was used to test effects of anti-coagulation (enoxaparin, rivaroxaban) therapy.

Results: 10 000 SiHa cells per mL induced rapid (5-6 min) aggregation of washed human platelets in presence of calcium (2 mM) and 1% of platelet free plasma (PFP). MCF-7 and SH-SY5Y cells also induced platelet aggregation, but with increased lag-time (2-fold for MCF-7 and 5-fold for SH-SY5Y). The time of aggregation anti-correlated with PFP fraction or tumor cell concentration. Platelet inhibition with apyrase or aspirin decreased the time of aggregation to 4 min, while inhibition with PGI2 or monafram increased it to 7-8 min. Platelet fixation did not significantly change the time of aggregation. Thrombin inhibition completely abolished platelet aggregation. Inhibition of fibrin polymerization with GPRP delayed aggregation of live platelet and prevented aggregation of fixed platelets. Confocal microscopy of platelet-tumor cell heteroaggregates confirmed that platelets were entrapped in the fibrin mesh without significant activation (measured by P-selectin exposure). In murine model of spontaneous metastasis anticoagulation started on the fifth day reduced the number of lung metastases ten-fold.

Conclusion(s): Tumor metastasis could be dependent on fibrin mesh formation around tumor cell, where inactive platelets get entrapped and thus shield the cell from immune recognition.
Funding. The study was supported by Russian Science Foundation grant 23-45-10039, and B23-RSF162.
Ethics. The study was performed in accordance with the Declaration of Helsinki and approved by the CTP PCP RAS ethics committee.