Unknown

Dataset Information

0

Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4.


ABSTRACT: Cell type transition occurs during normal development and under pathological conditions. In prostate cancer bone metastasis, prostate cancer-secreted BMP4 induces endothelial cell-to-osteoblast (EC-to-OSB) transition. Such tumor-induced stromal reprogramming supports prostate cancer progression. We delineate signaling pathways mediating EC-to-OSB transition using EC lines 2H11 and SVR. We found that BMP4-activated pSmad1-Notch-Hey1 pathway inhibits EC migration and tube formation. BMP4-activated GSK3β-βcatenin-Slug pathway stimulates Osx expression. In addition, pSmad1-regulated Dlx2 converges with the Smad1 and β-catenin pathways to stimulate osteocalcin expression. By co-expressing Osx, Dlx2, Slug and Hey1, we were able to achieve EC-to-OSB transition, leading to bone matrix mineralization in the absence of BMP4. In human prostate cancer bone metastasis specimens and MDA-PCa-118b and C4-2b-BMP4 osteogenic xenografts, immunohistochemical analysis showed that β-catenin and pSmad1 are detected in activated osteoblasts rimming the tumor-induced bone. Our results elucidated the pathways and key molecules coordinating prostate cancer-induced stromal programming and provide potential targets for therapeutic intervention.

SUBMITTER: Yu G 

PROVIDER: S-EPMC8086028 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5867603 | biostudies-literature
| S-EPMC3771343 | biostudies-literature
| S-EPMC5795617 | biostudies-literature
| S-EPMC4159670 | biostudies-literature
| S-EPMC8467999 | biostudies-literature
2021-12-21 | GSE162613 | GEO
| S-EPMC7874147 | biostudies-literature
| S-EPMC6795130 | biostudies-literature
| S-EPMC395917 | biostudies-literature
| S-EPMC7921109 | biostudies-literature