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

BIRKENSTOK CINTIA; CARRIERE PEDRO; NOVOA DIAZ MARÍA BELEN; ZWENGER ARIEL; GENTILI CLAUDIA; CALVO NATALIA

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2023

Cisplatin continues to be the main cytostatic used in the treatment ofcervical 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 characteristicsrelated to those found in the tumor microenvironment and bone morphogenetic protein 7 (BMP7) acting on these cells are involved inprocesses associated with cell plasticity in CC. This work aimed toevaluate the effect of these endothelial cells and BMP7 on chemoresistance to cisplatin in CC. First, the endothelial HMEC-1 cells weretreated for 24 hours with conditioned media from CC-derived HeLacells (TCM) to acquire the characteristics of endothelial cells foundin the niche of the tumor microenvironment. Then, the medium wasrenewed to obtain a new conditioned medium (ECM-T) and studythe release of soluble factors. The number of viable HeLa cells wascounted by trypan blue dye exclusion test to evaluate the effectsof cisplatin with or without ECM-T. We observed that these ECM-Tattenuated the cytotoxic effect of cisplatin in HeLa cells. The sameresult was obtained using the neutral red technique. Then, we studied if BMP7 released by tumor cells promotes characteristics similarto those of the tumor niche in endothelial cells. Using qRT-PCR, weobserved that exposure of HMEC-1 cells with TCM from HeLa cellsincreases the mRNA levels of endoglin, a protein overexpressedin tumor endothelial cells. This increase was partially reversed bypre-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 suggestan indirect role of BMP7 in the chemoresistance to cisplatin in CC byacting on endothelial cells