POTENTIAL ROLE OF ENDOTHELIAL CELLS AND BMP7 IN VASCULOGENIC MIMICRY FORMATION IN CERVICAL CANCER

BIRKENSTOK CINTIA; HOMMAN LUANA; CARRIERE PEDRO; NOVOA DÍAZ, MARÍA BELÉN; GENTILI CLAUDIA; CALVO NATALIA

Mar del Plata

Congreso; Reunión Conjunta SAIC. SAI. SAFIS 2022; 2022

Sociedad Argentina de Investigación Clínica (SAIC)

Vasculogenic mimicry (VM) is an alternative microvascular systemin which highly invasive tumor cells mimic endothelial cells by forming blood vessel-like structures. This process is correlated with poorprognosis, metastasis, and resistance to anti-angiogenic therapy invarious cancers, including cervical cancer (CC). We previously observed that after treatment with conditioned media from CC-derivedHeLa cells (TCMs) for 24 hours, HMEC-1 cells acquire characteristics related to endothelial cells found in the tumor microenvironment niche. In addition, we found that the signaling pathway of bonemorphogenetic protein 7 (BMP7) could be involved. The objectiveof this work was to investigate whether endothelial cells with characteristics related to those found in the tumor microenvironment areinvolved in the formation of VM in CC and the potential role of BMP7in this process. Initially, we evaluated whether the factors releasedby endothelial cells with characteristics related to those found in thetumor niche promote VM formation in CC. The HMEC-1 cells weretreated for 24 hours with TCM from HeLa cells, followed by a medium renewal to obtain a new conditioned medium (ECM-T). Using qRT-PCR, we observed that exposure of HeLa cells with theseECM-T increase the mRNA levels of markers associated with VM,VE-cadherin, EphA2 and vimentin. The protein-protein interactionnetwork by the STRING database identified interactions betweenBMP7 and 12 genes involved in MV formation. Furthermore, incubating HeLa cells with the ECM-T also promotes tube-like structureformation. These effects were partially reversed by pre-incubatingTCM from HeLa cells with an antibody against BMP7. These resultssuggest a potential indirect role of BMP7 in the VM in CC by acting on endothelial cells. Expanding the knowledge of the molecularmechanisms associated with VM in CC will help identify potentialbiomarkers that predict the prognosis and resistance to anti-angiogenic therapy.