| 1. |
- Hagberg Thulin, Malin, et al.
(författare)
-
Osteoblasts stimulate the osteogenic and metastatic progression of castration-resistant prostate cancer in a novel model for in vitro and in vivo studies.
- 2014
-
Ingår i: Clinical & experimental metastasis. - : Springer Science and Business Media LLC. - 1573-7276 .- 0262-0898. ; 31:3, s. 269-283
-
Tidskriftsartikel (refereegranskat)abstract
- Castration-resistant prostate cancer (CRPC) is strongly associated with sclerotic bone metastases and poor prognosis. Models that mimic human CRPC are needed to identify the mechanisms for prostate cancer (PC) growth in bone and to develop new therapeutic strategies. We characterize a new model, LNCaP-19, and investigate the interaction between tumor cells and osteoblasts in the sclerotic tumor response of CRPC. Osteogenic profiling of PC cell lines (LNCaP-19, LNCaP, C4-2B4, and PC-3) was performed by gene expression arrays and mineral staining. Conditioned medium from MC3T3-E1 was used for osteoblast stimulation of CRPC cells. The capacity of LNCaP-19 cells to induce sclerotic lesions was assessed in intratibial xenografts and verified by serum markers, histological analysis and bone mineral density (BMD) measurements. The CRPC cell line LNCaP-19 expresses a pronounced osteogenic profile compared to its parental androgen-dependent cell line LNCaP. Osteoblast-derived factors further increase the expression of genes known to enhance metastatic progression of PC. LNCaP-19 forms sclerotic tumors in tibia of castrated mice as evident by increased total BMD (P < 0.01). There was a strong correlation between serum osteocalcin and BMD (total: R (2) 0.811, P < 0.01, trabecular: R (2) 0.673, P < 0.05). For the first time we demonstrate that a CRPC cell line generated in vitro has osteogenic capacity and that osteomimicry can be an inherent feature of these cells. Osteoblast-derived factors further promote the osteogenic and metastatic phenotype in CRPC cells. Altogether, our model demonstrates that both tumor cells and osteoblasts are mediators of the bone forming process of CRPC.
|
|
| 2. |
- Huang, Junchi, et al.
(författare)
-
Osteoclasts directly influence castration-resistant prostate cancer cells
- 2022
-
Ingår i: Clinical and Experimental Metastasis. - : Springer Nature. - 0262-0898 .- 1573-7276. ; 39:5, s. 801-814
-
Tidskriftsartikel (refereegranskat)abstract
- Metastasis to bone is the leading cause of death from prostate cancer. Interaction between tumor cells and bone cells can promote progression and influence tumor phenotype. It is known that prostate cancer cells support osteoclast differentiation, and degradation of bone matrix by osteoclasts releases growth factors stimulating tumor cell proliferation and invasion. In the present study osteolytic (PC-3) and osteoblastic (LNCaP-19) castration-resistant prostate cancer (CRPC) cells were co-cultured with mature osteoclasts or their precursor cells (RAW 264.7) to characterize direct effects of mature osteoclasts on CRPC cells. Osteoclasts increased proliferation and decrease apoptosis of CRPC cells as assessed with flow cytometry. RNA sequencing revealed that osteolytic CRPC cells were more responsive to osteoclast stimulation regarding gene expression, but the overall induced expression patterns were similar between the prostate cancer cell lines. Genes related to DNA repair were upregulated by osteoclasts, while genes related to endoplasmic reticulum stress-induced apoptosis and cholesterol synthesis were downregulated. The results of this study shows that osteoclasts directly influence CRPC cells, increasing proliferation, decreasing apoptosis, and affecting gene expression pathways that can affect sensitivity to DNA damage and endoplasmic reticulum function. This suggests targeting of osteoclasts to be a possible way to affect efficacy of other drugs by combination regimens in treating prostate cancer metastases.
|
|
