Bi-directional interactions of prostate cancer cells and bone marrow endothelial cells in three-dimensional culture

The Prostate ◽  
2005 ◽  
Vol 64 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Jeffrey M. Barrett ◽  
Kathy A. Mangold ◽  
Tamas Jilling ◽  
Karen L. Kaul
The Prostate ◽  
2006 ◽  
Vol 66 (6) ◽  
pp. 632-650 ◽  
Author(s):  
Jeffrey M. Barrett ◽  
Mark A. Rovedo ◽  
Aamair M. Tajuddin ◽  
Tamas Jilling ◽  
Jill A. Macoska ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sukhneeraj P. Kaur ◽  
Arti Verma ◽  
Hee. K. Lee ◽  
Lillie M. Barnett ◽  
Payaningal R. Somanath ◽  
...  

AbstractCancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.


Author(s):  
Harri Makkonen ◽  
Jorma J. Palvimo

AbstractAndrogen receptor (AR) acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the level of genes and gene programs. Defective AR signaling leads to a wide array of androgen insensitivity disorders, and deregulated AR function, in particular overexpression of AR, is involved in the growth and progression of prostate cancer. Classic models of AR action view AR-binding sites as upstream regulatory elements in gene promoters or their proximity. However, recent wider genomic screens indicate that AR target genes are commonly activated through very distal chromatin-binding sites. This highlights the importance of long-range chromatin regulation of transcription by the AR, shifting the focus from the linear gene models to three-dimensional models of AR target genes and gene programs. The capability of AR to regulate promoters from long distances in the chromatin is particularly important when evaluating the role of AR in the regulation of genes in malignant prostate cells that frequently show striking genomic aberrations, especially gene fusions. Therefore, in addition to the mechanisms of DNA loop formation between the enhancer bound ARs and the transcription apparatus at the target core promoter, the mechanisms insulating distally bound ARs from promiscuously making contacts and activating other than their normal target gene promoters are critical for proper physiological regulation and thus currently under intense investigation. This review discusses the current knowledge about the AR action in the context of gene aberrations and the three-dimensional chromatin landscape of prostate cancer cells.


PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57706 ◽  
Author(s):  
Ediz Sariisik ◽  
Denitsa Docheva ◽  
Daniela Padula ◽  
Cvetan Popov ◽  
Jan Opfer ◽  
...  

1997 ◽  
Vol 75 (5) ◽  
pp. 634-638 ◽  
Author(s):  
T Deguchi ◽  
M Yang ◽  
H Ehara ◽  
S Ito ◽  
Y Nishino ◽  
...  

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