IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Heme oxygenase 1 alters the adhesive properties of prostate tumor cells growing in co culture with bone cells.
Autor/es:
ALEJANDRA PAEZ; ELBA VAZQUEZ; VALACCO PIA; ANSELMINO NICOLAS; GERALDINE GUERON
Lugar:
Sab Pablo
Reunión:
Conferencia; AACR-LACOG Translational Cancer Medicine; 2017
Resumen:
Prostate Cancer (PCa) is the second leading type of cancer in men. PCa cells display abnormalities in their adhesive properties which result in an augmented capacity to resist chemotherapy and colonize other organs such as bone. We have recently shown that heme­oxygenase 1 (HO­1) has a strong anti­tumoral effect in PCa through its interaction with cytoskeletal proteins, which regulate filopodia formation towards a more adhesive phenotype. Given the osteomimetic properties of PCa cells, we used a co-culture system where tumoral cells and bone cells share the medium but are not in direct physical contact. PC3 cells pre-treated or not with hemin (HO-1 pharmacological inducer, 50μM, 24h) were co cultured with the murine pre-osteoblastic (MC3T3) or pre-osteoclastic (RAW) cell line. The conditioned media (CM) from the co cultures were collected and added to new PC3 cultures in order to study changes in tumor cells adhesiveness. After 24h with the different CM, cells were fixed and stained with rhodamine-phalloidin to analyze contact among cells and filopodia in each cell individually.Results show that the CM from the co culture between PC3 cells and MC3T3 or RAW cells have a negative impact both in the number of filopodia per cell and contacts among them. However, when PC3 cells were pre-treated with hemin prior to co-culture, the number of filopodia and cell contacts are reestablished. Interestingly, PC3 cells cultured with CM from the co-culture system displayed more covered area after 6h of exposure in a wound healing assay, compared to CM from co-cultures with PC3 cells pre-treated with hemin. Finally, to identify the released factors in the co culture responsible for changing the adhesive properties of PC3 cells, we performed a mass spectrometry analysis followed by gene ontology analysis using DAVID software. Our analysis revealed more than 30 proteins released differentially in the co-culture CM involved in the adhesiveness of the cell, such as cadherins (PCDHGA10, FAT4, CDH1, CDH10), collagen (COL2A1) and several proteins associated to cell detachment (GATAD2A, KANK2, BCAS3, CAMSAP1, EPPK1, FLNC, TMPPE).Altogether, our findings demonstrate that HO­1 modulation in PCa cells induces morphological changes towards a less invasive phenotype through different proteins released as a consequence of the communication between PCa and bone cells. These data also show the relevance of the cytoskeleton regulating proteins as potential therapeutic targets against the aggressive and metastatic disease.