INVESTIGADORES
VAZQUEZ Elba Susana
artículos
Título:
HMOX1 IS A PIVOTAL MODULATOR OF BONE TURN OVER AND REMODELING. MOLECULAR IMPLICATIONS FOR PROSTATE CANCER BONE METASTASIS.
Autor/es:
ANSELMINO NICOLAS; MICHAEL STARBUCK; LABANCA ESTEFANIA; COTIGNOLA JAVIER; NAVONE NORA; GUERON GERALDINE; ZENCLUSSEN A; VAZQUEZ ELBA
Revista:
ANTIOXIDANTS & REDOX SIGNALING
Editorial:
MARY ANN LIEBERT INC
Referencias:
Lugar: New York; Año: 2020
ISSN:
1523-0864
Resumen:
Aims: Bone is the most frequent site of prostate cancer (PCa) metastasis. Tumor cells interact with the bone microenvironment interrupting tissue balance. Heme oxygenase‐1 (HO‐1; encoded by Hmox1) appears as a potential target in PCa maintaining the cellularhomeostasis. Our hypothesis is that HO‐1 is implicated in bone physiology and modulate the communication with PCa cells. Here we aimed at: 1) assessing the physiological impact of Hmox1 gene Knock‐out (KO) on bone metabolism in vivo and 2) determining the alterations of the transcriptional landscape associated with tumorigenesis and bone remodeling in cells growing in co‐culture (PCa cells with primary mouse osteoblasts ?PMOs‐ from BALB/c Hmox1+/+, Hmox1+/‐ and Hmox1‐/‐ mice). Results: Histomorphometric analysis of Hmox1‐/‐ mice bones exhibited significantly decreased bone density withreduced remodeling parameters. A positive correlation between Hmox1 expression and Runx2, Col1a1, Csf1 and Opg genes was observed in PMOs. Flow cytometry studies revealed two populations of PMOs with different ROS levels. The high‐ROS population was increased in PMOs Hmox1+/‐ compared with Hmox1+/+, but was significantly reduced in PMOs Hmox1‐/‐, suggesting restrained ROS tolerance in KO cells. Gene expression was altered in PMOs upon co‐culture with PCa cells, showing a pro‐osteoclastic profile. Moreover, HO‐1 induction in PCa cells growing in co‐culture with PMOs resulted in a significant modulation of key bone markers such as PTHrP and OPG. Innovation and Conclusion: We here demonstrate the direct implications of HO‐1 expression in bone remodeling and how it participates in the alterations in the communication between bone and prostate tumor cells.