PMID- 33334054
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210211
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 12
DP  - 2020 Dec 15
TI  - Stroma Transcriptomic and Proteomic Profile of Prostate Cancer Metastasis 
      Xenograft Models Reveals Prognostic Value of Stroma Signatures.
LID - 10.3390/cancers12123786 [doi]
LID - 3786
AB  - Resistance acquisition to androgen deprivation treatment and metastasis 
      progression are a major clinical issue associated with prostate cancer (PCa). The 
      role of stroma during disease progression is insufficiently defined. Using 
      transcriptomic and proteomic analyses on differentially aggressive 
      patient-derived xenografts (PDXs), we investigated whether PCa tumors predispose 
      their microenvironment (stroma) to a metastatic gene expression pattern. RNA 
      sequencing was performed on the PCa PDXs BM18 (castration-sensitive) and LAPC9 
      (castration-resistant), representing different disease stages. Using 
      organism-specific reference databases, the human-specific transcriptome (tumor) 
      was identified and separated from the mouse-specific transcriptome (stroma). To 
      identify proteomic changes in the tumor (human) versus the stroma (mouse), we 
      performed human/mouse cell separation and subjected protein lysates to 
      quantitative Tandem Mass Tag labeling and mass spectrometry. Tenascin C (TNC) was 
      among the most abundant stromal genes, modulated by androgen levels in vivo and 
      highly expressed in castration-resistant LAPC9 PDX. The tissue microarray of 
      primary PCa samples (n = 210) showed that TNC is a negative prognostic marker of 
      the clinical progression to recurrence or metastasis. Stroma markers of 
      osteoblastic PCa bone metastases seven-up signature were induced in the stroma by 
      the host organism in metastatic xenografts, indicating conserved mechanisms of 
      tumor cells to induce a stromal premetastatic signature. A 50-gene list stroma 
      signature was identified based on androgen-dependent responses, which shows a 
      linear association with the Gleason score, metastasis progression and 
      progression-free survival. Our data show that metastatic PCa PDXs, which differ 
      in androgen sensitivity, trigger differential stroma responses, which show the 
      metastasis risk stratification and prognostic biomarker potential.
FAU - Karkampouna, Sofia
AU  - Karkampouna S
AUID- ORCID: 0000-0002-1716-5237
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
FAU - De Filippo, Maria R
AU  - De Filippo MR
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
FAU - Ng, Charlotte K Y
AU  - Ng CKY
AUID- ORCID: 0000-0002-6100-0026
AD  - Oncogenomics Laboratory, Department for BioMedical Research, University of Bern, 
      Murtenstrasse 40, 3008 Bern, Switzerland.
FAU - Klima, Irena
AU  - Klima I
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
FAU - Zoni, Eugenio
AU  - Zoni E
AUID- ORCID: 0000-0002-3070-7694
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
FAU - Spahn, Martin
AU  - Spahn M
AD  - Lindenhofspital Bern, Prostate Center Bern, 3012 Bern, Switzerland.
FAU - Stein, Frank
AU  - Stein F
AD  - Proteomics Core Facility, EMBL Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, 
      Germany.
FAU - Haberkant, Per
AU  - Haberkant P
AUID- ORCID: 0000-0002-5608-9062
AD  - Proteomics Core Facility, EMBL Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, 
      Germany.
FAU - Thalmann, George N
AU  - Thalmann GN
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
AD  - Department of Urology, Inselspital, Anna Seiler Haus, Bern University Hospital, 
      3010 Bern, Switzerland.
FAU - Kruithof-de Julio, Marianna
AU  - Kruithof-de Julio M
AUID- ORCID: 0000-0002-6085-7706
AD  - Urology Research Laboratory, Department for BioMedical Research, University of 
      Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
AD  - Department of Urology, Inselspital, Anna Seiler Haus, Bern University Hospital, 
      3010 Bern, Switzerland.
LA  - eng
GR  - 748836/European Union Horizon 2020, Research and Innovation, Marie 
      Sklodowska-Curie/
PT  - Journal Article
DEP - 20201215
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7768471
OTO - NOTNLM
OT  - patient-derived xenografts
OT  - prostate cancer
OT  - stroma signature
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/19 06:00
MHDA- 2020/12/19 06:01
PMCR- 2020/12/15
CRDT- 2020/12/18 01:02
PHST- 2020/12/01 00:00 [received]
PHST- 2020/12/10 00:00 [accepted]
PHST- 2020/12/18 01:02 [entrez]
PHST- 2020/12/19 06:00 [pubmed]
PHST- 2020/12/19 06:01 [medline]
PHST- 2020/12/15 00:00 [pmc-release]
AID - cancers12123786 [pii]
AID - cancers-12-03786 [pii]
AID - 10.3390/cancers12123786 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Dec 15;12(12):3786. doi: 10.3390/cancers12123786.