Reference - Detail
| RRC ID | 62160 |
|---|---|
| Author | Shimabukuro K, Ichinose S, Koike R, Kubota T, Yamaguchi M, Miyasaka M, Aso T. |
| Title | Hepatocyte growth factor/scatter factor is implicated in the mode of stromal invasion of uterine squamous cervical cancer. |
| Journal | Gynecol Oncol |
| Abstract |
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. |
| Volume | 83(2) |
| Pages | 205-15 |
| Published | 2001-11-1 |
| DOI | 10.1006/gyno.2001.6347 |
| PII | S0090-8258(01)96347-4 |
| PMID | 11606073 |
| MeSH | Actins / biosynthesis Adenocarcinoma / metabolism Adenocarcinoma / pathology Cadherins / biosynthesis Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Adhesion Molecules / biosynthesis Cell Movement / physiology Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique HeLa Cells Hepatocyte Growth Factor / biosynthesis Hepatocyte Growth Factor / genetics Hepatocyte Growth Factor / physiology* Humans Neoplasm Invasiveness RNA, Messenger / biosynthesis RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Stromal Cells / metabolism Stromal Cells / pathology Tumor Cells, Cultured Uterine Cervical Neoplasms / metabolism Uterine Cervical Neoplasms / pathology* |
| IF | 4.623 |
| Resource | |
| Human and Animal Cells | HeLa.S3(RCB0191) |