PhD Scientific Days 2025

Poster Session III. - K: Theoretical and Translational Medicine

Pathological Role of Fibrin(ogen) in the Tumor Microenvironment under modulated Electro-Hyperthermia (mEHT) Treatment in a Triple Negative Breast Cancer (TNBC) Mouse Model.

Name of the presenter

Al-murshidy Hakim Bahlok Jebur

Institute/workplace of the presenter

Institute of Translational Medicine, Semmelweis University.

Authors

Hakim Bahlok Jebur Al-murshidy¹, Dániel Bócsi¹, Mohamed I. Elsalahaty¹, Qusay O. Abdalla¹, Yibo Go¹, Zoltán Koós¹, Eslam Abdalalem¹, Pedro Henrique Leroy Viana¹, Csaba András Schvarcz¹

1: Semmelweis University, Institute of Translational Medicine, 1094 Budapest, Tűzoltó u. 37-47.

Text of the abstract

Introduction: Effective therapy of triple-negative breast cancer (TNBC) has not yet been achieved. mEHT is a novel therapeutic approach based on selective heating and energy transfer to the tumor tissue using an electromagnetic field. mEHT induces tumor cell stress and may elicit a protective response within the tumor microenvironment (TME). Fibrinogen may play a non-canonical role when locally produced by cancer cells, particularly during mEHT treatment, potentially influencing the TME in distinct ways. Fibrinogen interacts with the integrin receptor αMβ2 (Mac-1) on myeloid cells, leads to leukocyte adhesion, migration, and the production of pro-inflammatory cytokines within TME.
Aim: To investigate how mEHT modulates fibrin(ogen) expression and its impact on inflammation and immune cell recruitment in the TNBC TME.
Methods: We analyzed transcriptomic data acquired from a previous murine TNBC model following mEHT treatment. Mouse TNBC 4T1 cells were inoculated orthotopically into female BALB/c mice. Tumor growth was measured by digital caliper and ultrasound. Expression of fibrinogen subunit genes (Fga, Fgb, Fgg) and inflammation-associated genes were assessed. qPCR validation of fibrinogen-related and inflammatory gene expression is in progress.
Result: qPCR validation of fibrinogen-related and inflammatory genes is currently underway. It is anticipated that repeated mEHT treatment will lead to a marked upregulation of stress-associated genes such as FGG, FGB, and FGA. Correspondingly, increased expression of inflammatory markers like Il-6 and Itgam1 (CD11b) is also expected in mEHT-treated tumors. These findings would support the idea that while mEHT exerts therapeutic pressure on tumors, it may also trigger a stress response that increases fibrinogen and pro-inflammatory factors in the tumor microenvironment.
Conclusion: It is anticipated that mEHT treatment will not only suppress tumor growth and proliferation in TNBC but also induce a stress-associated transcriptional response, characterized by upregulation of fibrinogen genes (FGG, FGB, FGA) and inflammatory markers (Il-6, Itgam/CD11b). This response is expected to result in increased fibrinogen deposition and immune cell recruitment within the tumor microenvironment (TME), potentially contributing to extracellular matrix remodeling and tumor adaptation.
Funding: SE250-2025-109.