PMID- 27775699
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2157-9024 (Print)
IS  - 2157-9024 (Electronic)
IS  - 2157-9024 (Linking)
VI  - 5
IP  - 10
DP  - 2016 Oct 24
TI  - SUSD2 expression in high-grade serous ovarian cancer correlates with increased 
      patient survival and defective mesothelial clearance.
PG  - e264
LID - 10.1038/oncsis.2016.64 [doi]
AB  - The cause of death among the majority of epithelial ovarian cancer (EOC) patients 
      involves passive dissemination of cancer cells within the peritoneal cavity and 
      subsequent implantation of cancer spheroids into adjacent organs. Thus, it is 
      important to identify the factors that mediate EOC metastasis and implantation, 
      including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes 
      a type I transmembrane protein containing several functional domains inherent to 
      adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 
      in several subtypes of EOC, with the strongest staining observed in high-grade 
      serous ovarian carcinomas (HGSOCs). A high-density, clinically annotated HGSOC 
      tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors 
      that had a low percentage of SUSD2 staining cells had a shorter median survival 
      (31.7 months) compared with patients who had tumors with extensive SUSD2 staining 
      (49.1 months; P-value=0.0083). To investigate the role of SUSD2 in HGSOCs, stable 
      OVCAR3, OVSAHO and KURAMOCHI cell lines were established with knockdown (KD) or 
      non-targeting (NT) of SUSD2. Boyden chamber and wound-healing assays demonstrated 
      that OVCAR3, OVSAHO and KURAMOCHI SUSD2-KD cells migrated at significantly higher 
      rates compared with their SUSD2 NT counterpart cell lines. Quantitative reverse 
      transcription-PCR and western immunoblot analysis indicated an inverse 
      relationship between SUSD2 and well-characterized mesenchymal proteins, including 
      Twist-1, Zeb-1, N-cadherin, STEAP1, AHNAK, Snail-1, COL5A2 and Snail-3 in OVCAR3, 
      OVSAHO and KURAMOCHI cell line models. In addition, OVCAR3 and KURAMOCHI SUSD2-KD 
      spheroids displayed increased mesothelial clearance ability compared with cells 
      that express endogenous levels of SUSD2. These data suggest that SUSD2 has a role 
      in the inhibition of mesothelial clearance, which is required for metastasis. 
      Altogether, our findings indicate that SUSD2 impedes migration, 
      epithelial-to-mesenchymal transitional and mesothelial clearance of HGSOC cells, 
      consistent with prolonged survival of patients with SUSD2-expressing tumors.
FAU - Sheets, J N
AU  - Sheets JN
AD  - Cancer Biology Research Center, Sanford Research, Sanford School of Medicine of 
      the University of South Dakota, Sioux Falls, SD, USA.
FAU - Iwanicki, M
AU  - Iwanicki M
AD  - Department of Cell Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Liu, J F
AU  - Liu JF
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, USA.
FAU - Howitt, B E
AU  - Howitt BE
AD  - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Hirsch, M S
AU  - Hirsch MS
AD  - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Gubbels, J A A
AU  - Gubbels JA
AD  - Department of Biology, Augustana College, Sioux Falls, SD, USA.
FAU - Drapkin, R
AU  - Drapkin R
AD  - Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, 
      University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
FAU - Egland, K A
AU  - Egland KA
AD  - Cancer Biology Research Center, Sanford Research, Sanford School of Medicine of 
      the University of South Dakota, Sioux Falls, SD, USA.
LA  - eng
GR  - P20 GM103548/GM/NIGMS NIH HHS/United States
GR  - P20 GM103620/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20161024
PL  - United States
TA  - Oncogenesis
JT  - Oncogenesis
JID - 101580004
PMC - PMC5117850
EDAT- 2016/10/25 06:00
MHDA- 2016/10/25 06:01
PMCR- 2016/10/01
CRDT- 2016/10/25 06:00
PHST- 2016/03/10 00:00 [received]
PHST- 2016/08/08 00:00 [revised]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2016/10/25 06:01 [medline]
PHST- 2016/10/25 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - oncsis201664 [pii]
AID - 10.1038/oncsis.2016.64 [doi]
PST - epublish
SO  - Oncogenesis. 2016 Oct 24;5(10):e264. doi: 10.1038/oncsis.2016.64.