PMID- 22262311
OWN - NLM
STAT- MEDLINE
DCOM- 20121127
LR  - 20120911
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 228
IP  - 2
DP  - 2012 Oct
TI  - Loss of membrane-bound serine protease inhibitor HAI-1 induces oral squamous cell 
      carcinoma cells' invasiveness.
PG  - 181-92
LID - 10.1002/path.3993 [doi]
AB  - A loss of balance between cell membrane-associated proteases and their inhibitors 
      may underlie cancer invasion and metastasis. We analysed the roles of a membrane- 
      associated serine protease inhibitor, HAI-1, in oral squamous cell carcinoma 
      (OSCC). While membranous HAI-1 was widely observed in cancer cells of human OSCC 
      tissues, this was significantly reduced at the infiltrative invasion front. In 
      vitro, HAI-1 was detected in all eight OSCC cell lines examined, in which its 
      cognate membrane protease, matriptase was also expressed. HAI-1 expression 
      knock-down (KD) in OSCC lines, SAS and HSC-3, reduced the growth of both lines in 
      vitro but significantly enhanced SAS tumourigenicity in vivo, which was 
      accompanied by histological changes suggestive of the epithelial-mesenchymal 
      transition. Both HAI-1-KD lines also exhibited significantly enhanced migratory 
      capability, and membrane-associated but not truncated HAI-1 was required to 
      rescue this phenotype. Other OSCC lines (HSC-2, Sa3, Ca9-22) also showed enhanced 
      migration in response to HAI-1 KD. The enhanced migration is partly attributed to 
      dysregulation of matriptase, as simultaneous matriptase KD alleviated the 
      migration of HAI-1-KD cells. HAI-1 deficiency also altered the expression of 
      CD24, S100A4, CCND2 and DUSP6, all of which are involved in tumour progression. 
      While matriptase was involved in the increased CD24 expression associated with 
      HAI-1 deficiency, the protease appeared to be not responsible for the altered 
      expression of other genes. Therefore, a matriptase-independent mechanism for the 
      invasiveness associated with HAI-1 KD is also present. Together, these 
      observations suggest that HAI-1 has a crucial suppressive role in OSCC cell 
      invasiveness.
CI  - Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Baba, Takashi
AU  - Baba T
AD  - Section of Oncopathology and Regenerative Biology, Department of Pathology, 
      University of Miyazaki, Japan.
FAU - Kawaguchi, Makiko
AU  - Kawaguchi M
FAU - Fukushima, Tsuyoshi
AU  - Fukushima T
FAU - Sato, Yuko
AU  - Sato Y
FAU - Orikawa, Hiroshi
AU  - Orikawa H
FAU - Yorita, Kenji
AU  - Yorita K
FAU - Tanaka, Hiroyuki
AU  - Tanaka H
FAU - Lin, Chen-Yong
AU  - Lin CY
FAU - Sakoda, Sumio
AU  - Sakoda S
FAU - Kataoka, Hiroaki
AU  - Kataoka H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120418
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Proteinase Inhibitory Proteins, Secretory)
RN  - 0 (SPINT1 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (matriptase)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/metabolism/*secondary
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Lymph Nodes/pathology
MH  - Lymphatic Metastasis
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Middle Aged
MH  - Mouth Neoplasms/metabolism/*pathology
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Proteinase Inhibitory Proteins, Secretory/*deficiency
MH  - Serine Endopeptidases/genetics/metabolism
EDAT- 2012/01/21 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/01/21 06:00
PHST- 2011/09/27 00:00 [received]
PHST- 2011/12/29 00:00 [revised]
PHST- 2012/01/12 00:00 [accepted]
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1002/path.3993 [doi]
PST - ppublish
SO  - J Pathol. 2012 Oct;228(2):181-92. doi: 10.1002/path.3993. Epub 2012 Apr 18.