PB1407 - Colonization of fibrin clot formed by cancer cells in tumor microenvironment. A mechanism potentially related with resistance to the anticancer treatment

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

CH

Chi Mai Tran Huong

PhD student
Diagnostica STAGO
gennevilliers, Ile-de-France, France
NM

Noémie Mourot

PhD student
INSERM
Paris, Ile-de-France, France
BF

Beshoy Faltas

PhD student
INSERM
Paris, Ile-de-France, France
EM

Elisabeth Mbemba

engineer
INSERM
Paris, Ile-de-France, France
IE

Ismail Elalamy

Director of Hematology Department of Thrombosis Center, Tenon University Hospital
Medicine Sorbonne University
Paris, Ile-de-France, France
MS

Michele Sabbah

Directeur de Recherche
INSERM
Paris, Ile-de-France, France
JF

Jawed Fareed

Professor of Pathology and Laboratory Medicine
Loyola University Medical center
Maywood, Illinois, United States

Presenting Author(s)

Patrick Van Dreden, PhD

PhD clinical research manager
Clinical Research Department, Diagnostica Stago
Gennevilliers, Ile-de-France, France

Co-Author(s)

Grigorios Gerotziafas

Pr
Research Group "Cancer - Hemostasis - Angiogenesis" Thrombosis Center
Paris, Ile-de-France, France

Background: Cancer cells via Tissue Factor (TF) expression and release of TF-bearing microvesicles trigger thrombin generation (TG) leading to fibrin clot formation in their microenvironment. The fibrinolytic potential of cancer cells is a key property for invasion, migration and metastasis.

Aims: Investigation of the colonization of fibrin clot by cancer cells

Methods: Cells from pancreatic and breast cancer (BXPC3, MDA-MB231, MCF7), were put in contact with normal human platelet poor plasma (PPP) enriched with fluorescent fibrinogen. The concentrations of tPA and D-Dimer in conditional media were measured at 2h intervals for an observational period of 72h. Fluorescent microscopy was used for the study of cancer cell invasion in the fibrin network and MTT assay was used for the assessment of cell viability.

Results: BXPC3 and MDA-MB231 but not MCF7 cells expressed tPA. In the presence of BXPC3 and MDA-MB231 cells, within 20h, the concentration of tPA in the conditioned media significantly increased by 3- and 1.5-fold respectively and that of D-Dimers increased by 50 folds. D-Dimers expotentially increased until the end of the observation period. In the presence of MCF7 no significant increase of tPA and D-dimers was observed. Fluorescent microscopy analysis showed the presence of numerous clusters of BXPC3 or MDA-MB231 cells within the clot. Lower number of MCF7 clusters were discovered. Cancer cells of the intra-clot clusters were alive and migrated from the initial monolayer of the cell culture.

Conclusion(s): This study documents the presence of cancer cells clusters within the fibrin clot which is related with their constitutional capacity to express tPA and to induce fibrinolysis. Aggressive pancreatic and breast cancer cells possessed significant highly fibrinolytic potential. This proof-of-concept study provides evidence of a new mechanism which could contribute to the development of resistance to anticancer treatment.