Evidence for preferential adhesion of ovarian epithelial carcinoma cells to type I collagen mediated by the alpha2beta1 integrin.
Epithelial ovarian carcinoma, the leading cause of gynecologic cancer death, is characterized by widespread intra-abdominal metastases mediated primarily by surface shedding of tumor cells and peritoneal implantation. Whereas hematogenous metastasis is known to involve cellular adhesion, extracellular matrix proteolysis and cell migration, the role of these processes in the intraperitoneal dissemination of ovarian cancer remains unclear. To analyze further the role of adhesion and proteolysis in ovarian carcinoma dissemination, we have characterized the adhesive profiles of 4 primary cultures of ovarian carcinoma cells and 5 ovarian carcinoma cell lines. Our data demonstrate preferential adhesion of ovarian carcinoma cells to interstitial type I collagen. Analysis of adhesion molecule expression demonstrated the presence of the alpha2 and beta1 integrin subunits by cell surface ELISA, immunoprecipitation and immunohistochemistry. Furthermore, antibodies directed against the alpha2 and beta1 subunits inhibited adhesion of ovarian carcinoma cells to type I collagen by 56% and 95%, respectively. Plasminogen activator and matrix metalloproteinase production by adherent cells was not altered as a consequence of adhesion to individual extracellular matrix proteins; however, adhesion to an extracellular matrix comprised primarily of interstitial collagen increased plasminogen activator activity in 5 of 5 cell lines. Since the ovarian carcinoma micro-environment is rich in type I collagen, our data suggest that preferential adhesion to type I collagen followed by secretion of serine and metalloproteinases may represent a biochemical mechanism by which the intraperitoneal dissemination of ovarian carcinoma is mediated.
Moser
T L
TL
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Pizzo
S V
SV
Bafetti
L M
LM
Fishman
D A
DA
Stack
M S
MS
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D016023:Integrins / Q000502:physiology*; D008666:Metalloendopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000502:physiology; D010051:Ovarian Neoplasms / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D038981:Receptors, Collagen; D012697:Serine Endopeptidases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D016023:Integrins; D017395:Plasminogen Activator Inhibitor 1; D038981:Receptors, Collagen; D003094:Collagen; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases