Gonadotropin stimulation of MLS human epithelial ovarian carcinoma cells augments cell adhesion mediated by CD44 and by alpha(v)-integrin.
OBJECTIVE
The goal of this work was to evaluate the involvement of gonadotropins in the regulation of adhesion of human epithelial ovarian carcinoma. We studied two pathways that were previously implicated in the metastatic implantation of ovarian carcinoma to the peritoneum, namely hyaluronan-CD44 and RGD-integrin mediated adhesion.


METHODS
Two cell lines derived from human epithelial ovarian carcinoma (MLS and OC238) were stimulated with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH). Expression of CD44 was evaluated by Western blotting. Expression of alpha(v)-integrins was studied by RT-PCR and Northern blot. Integrin and CD44 mediated adhesion of the cells was analyzed using culture plates coated either with a thrombin derived RGD containing peptide or fibronectin for integrin mediated adhesion or with hyaluronan for CD44 mediated adhesion.


RESULTS
MLS cells stimulated with either LH or FSH showed increased adhesion to culture plates coated with hyaluronan, as well as to culture plates coated with fibronectin or with a thrombin derived RGD containing peptide. In these cells, gonadotropin stimulation led to induced expression of the integrin subunit alpha(v) and CD44, the cell surface hyaluronan receptor. On the other hand, OC238 cells showed no expression of the integrin subunit alpha(v) and no hormonal effect on the expression of CD44. Accordingly, adhesion of OC238 cells on either RGD or CD44 was not affected by hormonal stimulation.


CONCLUSIONS
Elevated levels of gonadotropins may in some cases facilitate peritoneal metastatic dissemination of ovarian cancer by increasing cell adhesion, the first essential step in the invasion process.
Schiffenbauer
Yael S
YS
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Meir
Gila
G
Maoz
Miriam
M
Even-Ram
Sharona Cohen
SC
Bar-Shavit
Rachel
R
Neeman
Michal
M
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000502:physiology*; D006820:Hyaluronic Acid / Q000494:pharmacology; D039564:Integrin alphaV; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018960:Hyaluronan Receptors; D039564:Integrin alphaV; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006820:Hyaluronic Acid