PMID- 11606073
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20051117
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 83
IP  - 2
DP  - 2001 Nov
TI  - Hepatocyte growth factor/scatter factor is implicated in the mode of stromal 
      invasion of uterine squamous cervical cancer.
PG  - 205-15
AB  - OBJECTIVE: The purpose of this study was to examine the relationship of 
      hepatocyte growth factor/scatter factor (HGF/SF) to cell motility and invasion in 
      uterine cervical cancer. METHODS: We examined the expression of HGF/SF and its 
      receptor, c-met, in cervical cancer cell lines SKG-IIIa (squamous cell carcinoma) 
      and Hela-S3 (adenocarcinoma) and in stromal cells of the cervical cancer tissue 
      by reverse transcription-polymerase chain reaction. We studied the effect of 
      HGF/SF on invasiveness of SKG-IIIa and Hela-S3 in an invasion model of the 
      modified Boyden chamber method and by electron microscopy. SKG-IIIa cells were 
      also seeded on the thick Matrigel-coated layer to evaluate the invasion patterns 
      in three-dimensional directions. To investigate the mechanism of an inductive 
      effect of HGF/SF on the invasiveness of SKG-IIIa, we examined the effect of 
      HGF/SF on the expression of intercellular adhesion molecule E-cadherin, 
      cell-substrate adhesion molecules CD44, alpha2beta1, and alpha6beta1, and 
      intracellular skeleton fiber actin in SKG-IIIa in cell enzyme-linked 
      immunosorbent assay (ELISA) and immunofluorescence staining. RESULTS: HGF/SF 
      messenger RNA (mRNA) was detected in stromal cells, and c-met mRNA was detected 
      in SKG-IIIa and Hela-S3. Hela-S3 that initially showed weak intercellular contact 
      freely invaded the Matrigel-coated multiporous membrane without the addition of 
      HGF/SF. In contrast, SKG-IIIa that initially showed strong intercellular adhesion 
      could invade the membrane after the addition of HGF/SF. The same results were 
      represented by an addition of HECD-1, an anti-human E-cadherin antibody. In an 
      experiment with cell culture in a thick Matrigel layer, control SKG-IIIa showed a 
      mirror-ball-like invasion pattern, whereas HGF/SF-stimulated SKG-IIIa spread 
      horizontally over the membrane and migrated through the membrane holes, 
      presenting a tentacular invasion pattern. Migration of SKG-IIIa under the 
      membrane was confirmed by scanning and transmission electron microscopy. The 
      addition of HGF/SF in cell ELISA assay decreased the expression of E-cadherin and 
      actin in SKG-IIIa, but it did not change the expression of CD44, alpha2beta1, and 
      alpha6beta1. Immunofluorescence staining revealed that the expression of 
      E-cadherin in cell membrane was disturbed by HGF/SF. CONCLUSIONS: Our data 
      indicate that HGF/SF produced by stromal cells influences the mode of stromal 
      invasion of squamous cervical cancer by selectively decreasing the expression of 
      both E-cadherin and actin.
CI  - Copyright 2001 Academic Press.
FAU - Shimabukuro, K
AU  - Shimabukuro K
AD  - Comprehensive Reproductive Medicine, Graduate School, Tokyo, Japan. 
      shima-hs@d9.dion.ne.jp
FAU - Ichinose, S
AU  - Ichinose S
FAU - Koike, R
AU  - Koike R
FAU - Kubota, T
AU  - Kubota T
FAU - Yamaguchi, M
AU  - Yamaguchi M
FAU - Miyasaka, M
AU  - Miyasaka M
FAU - Aso, T
AU  - Aso T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Actins)
RN  - 0 (Cadherins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (RNA, Messenger)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Actins/biosynthesis
MH  - Adenocarcinoma/metabolism/pathology
MH  - Cadherins/biosynthesis
MH  - Carcinoma, Squamous Cell/metabolism/*pathology
MH  - Cell Adhesion Molecules/biosynthesis
MH  - Cell Movement/physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - HeLa Cells
MH  - Hepatocyte Growth Factor/biosynthesis/genetics/*physiology
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stromal Cells/metabolism/pathology
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/metabolism/*pathology
EDAT- 2001/10/19 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/19 10:00
PHST- 2001/10/19 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/19 10:00 [entrez]
AID - S0090-8258(01)96347-4 [pii]
AID - 10.1006/gyno.2001.6347 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2001 Nov;83(2):205-15. doi: 10.1006/gyno.2001.6347.