Relation between laminin-5 gamma 2 chain and cell surface metalloproteinase MT1-MMP in clear cell carcinoma of the ovary.
Ovarian clear cell carcinoma (CCC) characteristically shows stromal accumulation of the basement membrane material laminin-5 (LN-5). LN-5 works not only as a substrate for cell anchorage but also as a stimulator for cell migration. Our previous study showed that CCC cell increased migration over excessive LN-5 in vitro. However, it remains unclear why LN-5 rather promotes cell migration than cell anchorage. A recent study has shown that the processing of the LN-5 gamma 2 chain by membrane type 1-matrix metalloproteinase (MT1-MMP) was responsible for increasing cell migration activity but reducing cell anchoring activity of LN-5. In the present study, 3 CCC cell lines were examined for LN-5 gamma 2 chain levels by Western blotting. Processed gamma 2 chain (105 kDa) was detected in the extracellular matrix of all 3 CCC cell lines in vitro. Immunocytochemically they expressed MT1-MMP on the cell surface. In surgical specimens, 22 of 30 (73%) CCCs showed membranous expression of MT1-MMP, and stromal accumulation of the LN-5 gamma 2 chain, especially in the area of papillary architecture. These results indicate that proteolytic processing of the LN-5 gamma 2 chain by MT1-MMP is involved in cell migration and subsequent architectural organization in ovarian CCC.
Kato
Noriko
N
Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan. nkato@med.id.yamagata-u.ac.jp
Motoyama
Teiichi
T
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology
C400567:LAMC2 protein, human; D007797:Laminin; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14