ROLE OF ENDOTHELIAL CELLS AND BMP7 IN CISPLATIN CHEMORESISTANCE OF CERVICAL CANCER CELLS

BIRKENSTOK C; CARRIERE P; NOVOA DÍAZ MB; ZWENGER A; GENTILI C; CALVO N

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC).; 2023

Sociedad Argentina de Investigación Clínica (SAIC).

Cisplatin continues to be the main cytostatic used in the treatment of cervical cancer (CC), despite its use, a significant population develops chemoresistance both at the beginning and during the disease. The interaction between tumor cells and their tumor microenvironment, through soluble factors, may be related to said resistance. We previously observed that endothelial cells with characteristics related to those found in the tumor microenvironment and bone morphogenetic protein 7 (BMP7) acting on these cells are involved in processes associated with cell plasticity in CC. This work aimed to evaluate the effect of these endothelial cells and BMP7 on chemoresistance to cisplatin in CC. First, the endothelial HMEC-1 cells were treated for 24 hours with conditioned media from CC-derived HeLa cells (TCM) to acquire the characteristics of endothelial cells found in the niche of the tumor microenvironment. Then, the medium wasrenewed to obtain a new conditioned medium (ECM-T) and study the release of soluble factors. The number of viable HeLa cells was counted by trypan blue dye exclusion test to evaluate the effectsof cisplatin with or without ECM-T. We observed that these ECM-T attenuated the cytotoxic effect of cisplatin in HeLa cells. The same result was obtained using the neutral red technique. Then, we studied if BMP7 released by tumor cells promotes characteristics similar to those of the tumor niche in endothelial cells. Using qRT-PCR, we observed that exposure of HMEC-1 cells with TCM from HeLa cells increases the mRNA levels of endoglin, a protein overexpressed in tumor endothelial cells. This increase was partially reversed by pre-incubating TCM with an antibody against BMP7. The neutralizing of BMP7 with an antibody also attenuated the response of HeLacells to EMC-T in the presence of cisplatin. These results suggest an indirect role of BMP7 in the chemoresistance to cisplatin in CC by acting on endothelial cells.