| Project/Area Number |
08671911
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE |
|---|
Principal Investigator |
FUJII Miho ASSISITANT PROFESSOR OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE, 医学部, 講師 (00260761)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KUDO Ryuichi PROFESSOR OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE, 医学部, 教授 (70045409)
SAWADA Norimasa ASSISTANT PROFESSOR OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE, 医学部, 助教授 (30154149)
SAGAE Satoru ASSISTANT PROFESSOR OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE, 医学部, 講師 (00187056)
ENDO Toshiaki ASSISTANT PROFESSOR OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE, 医学部, 講師 (90213595)
MORI Satoko STUDENT OF SAPPORO MEDICAL UNIVERSITY,SCHOOL OF MEDICINE
|
|---|
| Project Period (FY) |
1996 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | UTERINE ADENOMYOSIS / UTERINE ADENOCARCINOMA / MATRIX METALLOPROTEINASE (MMP) / MMP-7 / MMP-2 / MMP-9 / INVASION ASSAY / IN SITU HYBRIDISATION / Matrix metalloproteinase(MMP) / pump-1 / MMP / in situ hybridization / zymography / 子宮内膜症 / MMP7 / 子宮腺筋癌 / 子宮内膜 / 浸潤 |
|---|
| Research Abstract |
Uterine adenomyosis is a benign invasive growth of functioning endometrial tissue (consisting of endometrial glands and stroma) into the myometrium, causing its derangement and disintegration. Although benign disease, adenomyosis is often associated with complications including dysmenorrhea and infertility that require medical interventions. The invasion of adenomyosis into the myometrium is comparable to that of uterine adenocarcinoma in terms of the cellular mobility and the expression of matrix metalloproteinases (MMPs), a multi-gene family of enzymes whose substrates are extracellular matrix components. In our previous study in an animal model for adenomyosis uteri induced in pituitary-grafted mice, gelatin zymography identified several distinct enzyme activities of MMPs in extracts obtained from a uterus with invasive adenomyosis, whereas no enzyme activities of MMPs were demonstrated in those obtained from normal uterus, suggesting the involvement of several MMPs in the developme
… More
nt of adenomyosis. In the present study, we investigated the invasive ability and the expression of MMPs in the cells of human uterine adenomyosis and uterine adenocarcinoma.
A collagen gel invasion assay showed that cell cultures from uterine adenocarcinoma cell line were highly invasive, those from adenomyosis uteri were moderately invasive, those from normal uterine stroma had some invasive ability and those from normal uterine gland had no invasive ability. In situ zymography demonstrated that gelalinase-activity was present in adenomyosis uteri and uterine adenocarcinoma, whereas no gelatinase activity was present in normal uterine endometrium. Western blot analysis of the immunoreactive MMP-7 showed that higher amounts of MMP-7 were observed in the uterine adenocarcinoma compared with those in the epithelial cells of uterine adenomyosis, whereas almost no amounts were present in those of normal uterine endomeirium. However, in the same samples with those used in the study on the expression of the immunoreactive MMP-7, a band of 440 bp PCR product was present in comparable amounts in both adenomyosis and normal uterine endometrium, suggesting the involvement of a post-transcriptional modification in the enhanced enzyme activity of MMP-7 observed in adenomyosis. Immunohistochemical study showed that immunoreactive MMP-7 was present on the glandular cells of uterine adenocarcinoma, adenomyosis uteri and normal uterine endometrium, but not on the stromal cells of these tissues. Higher amounts of immunoreactive MMP-7 were present in adenocarcinoma and adenomyosis than in normal uterine endometrium in proliferative phase, whereas immunoreactive MMP-7 was absent in normal uterine endometrium in secretory phase. Immunoreactive MMP-2 and MMP-9 were present in both glandular cells and stromal cells in uterine adenocarcinoma and adenomyosis, whereas those in normal uterine endometrium were almost absent in stromal cells whether in proliferative phase or secretory phase. An in situ hybridization study showed that MMP-7 mRNA intra-cellular expression was different according to the tissues used : that in uterine adenocarcinoma cells was homogenous in cytoplasm ; that in adenomyosis uteri was homogenous in cytoplasm in some cells and was localized at the apical site in other cells ; that in normal uterine endometrium was localized at the apical site of the cells. The expressions of MMP-2 and MMP-9 mRNAs by in situ hybridization were also characteristic according to the tissues used : MMP-2 and MMP-9 mRNAs in uterine adenocarcinoma cells were present both in glandular cells and stromal cells, with highly expressive and less expressive glandular cells mixed ; those in adenomyosis uteri were expressed in the stromal cells adjacent to the glandular cells ; those in normal endometrium were almost absent in the stromal cells and the glandular cells whether in proliferative phase or secretory phase.
The present study suggests that ectopic endometrial cells of adenomyosis may be somewhere between normal cells and adenocarcinoma cells in terms of the invasive ability and the expression of MMPs, and is compatible with an idea that the glandular expression of MMP-7 is associated with the expression of MMP-2 and MMP-9 in the stromal cells that preced the invasion of endometrial glandular cells into the myometrium and proceed through loose connective tissues in the myometrium. Less
|
