PMID- 30862717
OWN - NLM
STAT- Publisher
LR  - 20190329
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
DP  - 2019 Mar 12
TI  - Collagen remodeling in the hypoxic tumor-mesothelial niche promotes ovarian
      cancer metastasis.
LID - canres.2616.2018 [pii]
LID - 10.1158/0008-5472.CAN-18-2616 [doi]
AB  - Peritoneal metastases are the leading cause of morbidity and mortality in
      high-grade serous ovarian cancer (HGSOC). Accumulating evidence suggests that
      mesothelial cells are an important component of the metastatic microenvironment
      in HGSOC. However, the mechanisms by which mesothelial cells promote metastasis
      are unclear. Here we report that the HGSOC tumor-mesothelial niche was hypoxic
      and hypoxic signaling enhanced collagen I deposition by mesothelial cells.
      Specifically, hypoxic signaling increased expression of lysyl oxidase (LOX) in
      mesothelial and ovarian cancer cells to promote collagen crosslinking and tumor
      cell invasion. The mesothelial niche was enriched with fibrillar collagen in
      human and murine omental metastases. Pharmacologic inhibition of LOX reduced
      tumor burden and collagen remodeling in murine omental metastases. These findings
      highlight an important role for hypoxia and mesothelial cells in the modification
      of the extracellular matrix and tumor invasion in HGSOC.
CI  - Copyright (c)2019, American Association for Cancer Research.
FAU - Natarajan, Suchitra
AU  - Natarajan S
AD  - Radiation Oncology, Stanford University.
FAU - Foreman, Kaitlyn M
AU  - Foreman KM
AD  - Radiation Oncology, Stanford University.
FAU - Soriano, Michaela I
AU  - Soriano MI
AUID- ORCID: https://orcid.org/0000-0002-0689-4848
AD  - Radiation Oncology, Stanford University.
FAU - Rossen, Ninna S
AU  - Rossen NS
AD  - Radiation Oncology, Stanford University.
FAU - Shehade, Hussein
AU  - Shehade H
AD  - Radiation Oncology, Stanford University.
FAU - Fregoso, Daniel R
AU  - Fregoso DR
AUID- ORCID: https://orcid.org/0000-0001-5173-0773
AD  - Radiation Oncology, Stanford University.
FAU - Eggold, Joshua T
AU  - Eggold JT
AD  - Radiation Oncology, Stanford University.
FAU - Krishnan, Venkatesh
AU  - Krishnan V
AD  - Obstetrics and Gynecology, Stanford University.
FAU - Dorigo, Oliver
AU  - Dorigo O
AD  - Obstetrics and Gynecology/Gynecologic Oncology, Stanford University.
FAU - Krieg, Adam J
AU  - Krieg AJ
AUID- ORCID: https://orcid.org/0000-0002-3069-0378
AD  - Obstetrics and Gynecology, Oregon Health and Science University.
FAU - Heilshorn, Sarah C
AU  - Heilshorn SC
AD  - Materials Science and Engineering, Stanford University.
FAU - Sinha, Subarna
AU  - Sinha S
AD  - Biosciences Division, Stanford Research Institute.
FAU - Fuh, Katherine C
AU  - Fuh KC
AD  - Obstetrics and Gynecology, Washington University.
FAU - Rankin, Erinn B
AU  - Rankin EB
AD  - Radiation Oncology and Obstetrics & Gynecology, Stanford University
      erankin@stanford.edu.
LA  - eng
GR  - R01 CA198291/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20190312
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
EDAT- 2019/03/14 06:00
MHDA- 2019/03/14 06:00
CRDT- 2019/03/14 06:00
PHST- 2019/03/05 00:00 [accepted]
PHST- 2018/08/22 00:00 [received]
PHST- 2018/12/27 00:00 [revised]
PHST- 2019/03/14 06:00 [entrez]
PHST- 2019/03/14 06:00 [pubmed]
PHST- 2019/03/14 06:00 [medline]
AID - 0008-5472.CAN-18-2616 [pii]
AID - 10.1158/0008-5472.CAN-18-2616 [doi]
PST - aheadofprint
SO  - Cancer Res. 2019 Mar 12. pii: 0008-5472.CAN-18-2616. doi:
      10.1158/0008-5472.CAN-18-2616.