PMID- 34845375
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20230209
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 41
IP  - 6
DP  - 2022 Feb
TI  - Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes 
      prostate cancer metastasis through YAP/TAZ inhibition.
PG  - 757-769
LID - 10.1038/s41388-021-02131-7 [doi]
AB  - Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that 
      enhance PCa progression. How tumor-induced bone formation enhances PCa 
      progression is not known. We have previously shown that PCa-induced bone 
      originates from endothelial cells (ECs) that have undergone 
      endothelial-to-osteoblast (EC-to-OSB) transition by tumor-secreted bone 
      morphogenetic protein 4 (BMP4). Here, we show that EC-to-OSB transition leads to 
      changes in the tumor microenvironment that increases the metastatic potential of 
      PCa cells. We found that conditioned medium (CM) from EC-OSB hybrid cells 
      increases the migration, invasion, and survival of PC3-mm2 and C4-2B4 PCa cells. 
      Quantitative mass spectrometry (Isobaric Tags for Relative and Absolute 
      Quantitation) identified Tenascin C (TNC) as one of the major proteins secreted 
      from EC-OSB hybrid cells. TNC expression in tumor-induced OSBs was confirmed by 
      immunohistochemistry of MDA PCa-118b xenograft and human bone metastasis 
      specimens. Mechanistically, BMP4 increases TNC expression in EC-OSB cells through 
      the Smad1-Notch/Hey1 pathway. How TNC promotes PCa metastasis was next 
      interrogated by in vitro and in vivo studies. In vitro studies showed that a 
      TNC-neutralizing antibody inhibits EC-OSB-CM-mediated PCa cell migration and 
      survival. TNC knockdown decreased, while the addition of recombinant TNC or TNC 
      overexpression increased migration and anchorage-independent growth of PC3 or 
      C4-2b cells. When injected orthotopically, PC3-mm2-shTNC clones decreased 
      metastasis to bone, while C4-2b-TNC-overexpressing cells increased metastasis to 
      lymph nodes. TNC enhances PCa cell migration through alpha5beta1 integrin-mediated 
      YAP/TAZ inhibition. These studies elucidate that tumor-induced stromal 
      reprogramming generates TNC that enhances PCa metastasis and suggest that TNC may 
      be a target for PCa therapy.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Lee, Yu-Chen
AU  - Lee YC
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, 77030, USA.
FAU - Lin, Song-Chang
AU  - Lin SC
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, 77030, USA.
FAU - Yu, Guoyu
AU  - Yu G
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, 77030, USA.
FAU - Zhu, Ming
AU  - Zhu M
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA.
FAU - Song, Jian H
AU  - Song JH
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA.
FAU - Rivera, Keith
AU  - Rivera K
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
FAU - Pappin, Darryl J
AU  - Pappin DJ
AD  - Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, NY, USA.
FAU - Logothetis, Christopher J
AU  - Logothetis CJ
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA.
FAU - Panaretakis, Theocharis
AU  - Panaretakis T
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA.
FAU - Wang, Guocan
AU  - Wang G
AUID- ORCID: 0000-0002-8922-7249
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA.
FAU - Yu-Lee, Li-Yuan
AU  - Yu-Lee LY
AUID- ORCID: 0000-0002-2353-406X
AD  - Departments of Medicine and Molecular and Cellular Biology, Baylor College of 
      Medicine, Houston, TX, 77030, USA.
FAU - Lin, Sue-Hwa
AU  - Lin SH
AUID- ORCID: 0000-0002-6122-4054
AD  - Department of Translational Molecular Pathology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX, 77030, USA. slin@mdanderson.org.
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, 77030, USA. slin@mdanderson.org.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - P50 CA140388/CA/NCI NIH HHS/United States
GR  - R00 CA194289/CA/NCI NIH HHS/United States
GR  - P30 CA045508/CA/NCI NIH HHS/United States
GR  - R01 CA174798/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211129
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Tenascin)
SB  - IM
MH  - *Tenascin
PMC - PMC8818031
MID - NIHMS1758521
EDAT- 2021/12/01 06:00
MHDA- 2022/02/24 06:00
PMCR- 2022/05/29
CRDT- 2021/11/30 06:49
PHST- 2021/07/06 00:00 [received]
PHST- 2021/11/19 00:00 [accepted]
PHST- 2021/11/11 00:00 [revised]
PHST- 2021/12/01 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/11/30 06:49 [entrez]
PHST- 2022/05/29 00:00 [pmc-release]
AID - 10.1038/s41388-021-02131-7 [pii]
AID - 10.1038/s41388-021-02131-7 [doi]
PST - ppublish
SO  - Oncogene. 2022 Feb;41(6):757-769. doi: 10.1038/s41388-021-02131-7. Epub 2021 Nov 
      29.