OC 32.5 - CD146-positive tumors are associated with venous thromboembolism

Monday, July 11, 2022

11:45 AM – 12:00 PM

Location: ExCel Center, S11B

Presentation Format: Virtual

Presenting Author(s)

Ahmad Joshkon, PhD

Post-doctoral position
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France

Co-Author(s)

JS

Jimmy Stalin

Researcher
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
WT

Wael Traboulsi

Researcher
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
LV

Lucie Vivancos -Stalin

Researcher
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
MN

Marie Nollet

Researcher
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
RL

Romaric Lacroix, PharmD PhD

PharmD. PhD. - Professor of Immunology and Hematology
Aix-Marseille Univ, APHM, INSERM, INRAE, C2VN, Laboratory of Hematology and Vascular Biology, University Hospital La Conception, Marseille, France
Marseille, Provence-Alpes-Cote d'Azur, France
RB

Richard Bachelier

Ingenior
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
Françoise Dignat-George

Professor, Director at C2VN
Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
AB

Alexandrine Bertaud

Assistant professor
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
Aurélie leroyer, PhD

Assistant professor
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France
NB

Nathalie Bardin

Professor
Aix-Marseille Univ, APHM, INSERM, INRAE, C2VN -Laboratory of Hematology and Vascular Biology, University Hospital La Conception, Marseille, France.
Marseille, Provence-Alpes-Cote d'Azur, France
MB

Marcel Blot-Chabaud

Research director
INSERM/Aix-Marseille University
Marseille, Provence-Alpes-Cote d'Azur, France

Background: CD146 is a membrane glycoprotein physiologically present on all the vascular tree where it is involved in angiogenesis. Pathologically, CD146 is expressed by various tumors with a positive correlation between its expression and advanced cancer stages. First identified on melanoma cells, CD146 was thereafter found to be also expressed by many other cancers. In these tumors, CD146 and its secreted soluble form (sCD146), are involved in tumor growth, dissemination and in angiogenesis.

Aims: The aim of the study was to examine a potential role of CD146/sCD146 in cancer-associated thromboembolism and to test the effect of antibodies targeting the molecule.

Methods: Two highly metastatic CD146-positive cell lines, the ovarian HEY and melanoma A375, were used for in vitro and in vivo experiments.
In vivo, preclinical models of nude mice xenografted with both cell lines were generated and the effect of the anti-sCD146 antibody was tested by iv injection in the animals. RNA profiling was also performed to analyse differences between cancer cells treated with anti-sCD146 mAb and cells treated with control IgG.

Results: We show a direct effect of sCD146 on TF expression in cancer cells in vitro. sCD146 upregulated surface TF expression, increased soluble TF in the cells’ supernatant along with an increase in factor Xa and increased the generation of microparticles. In vivo, sCD146 induced venous thromboembolism. An anti-sCD146 antibody potently neutralized the adverse effect of sCD146 by decreasing the expression of genes related to thromboembolism and by reducing both the number of cancer microparticles and venous thromboembolism in mice.

Conclusion(s): We show a link between CD146 expression on the tumor cells and thrombotic events. Inhibiting the secreted form of CD146 with anti-sCD146 mAb reduced both tumor dissemination and venous thromboembolism, suggesting that the use of this antibody could be of therapeutic interest in the treatment of CD146-positive tumors.

No conflict of interest.