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

BIRKENSTOCK CINTIA; CARRIERE PEDRO MATÍAS; NOVOA DÍAZ BELEN; ZWENGER ARIEL; GENTILI, CLAUDIA; CALVO, NATALIA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Chemotherapy with cisplatin is one of the treatments for patients with advanced or recurrent cervical cancer (CC). Crosstalk between microenvironment cells and tumor cells through soluble factors can induce chemoresistance acquisition and thus compromise their use in clinical practice. 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. The aim of this work was to investigate whether these endothelial cells and BMP7 also favor 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 characteristics related to endothelial cells found in the tumor microenvironment niche. Then, we performed a medium renewal to obtain a new conditioned medium (ECM-T) and study if these cells release factors that promote chemoresistance to cisplatin in CC. The number of viable HeLa cells was counted by trypan blue dye exclusion test to evaluate the effects of 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 HeLa cells 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.