Ovarian cancer cell invasion is inhibited by paclitaxel.
Overproduction of matrix metalloproteinases (MMPs) and alterations in adhesive and migratory behavior are common characteristics of metastatic cancer cells. Ovarian cancer is a highly invasive type of malignancy. The effect of the antineoplastic drug paclitaxel on human ovarian cancer cell (Ovcar-3) invasion was studied using an in vitro invasion assay with reconstituted basement membrane. The effect of treatment with paclitaxel was also determined separately on certain invasion-associated events, such as the secretion of 72 kDa type IV collagenase (gelatinase A/MMP-2), the expression of the tissue inhibitor of metalloproteinase-2 (TIMP-2), cell attachment and migration. Ovcar-3 cell attachment, migration and in vitro invasion were significantly decreased after paclitaxel treatment (P = 0.02, P < 0.01 and P = 0.001, respectively) whereas no alteration in the secretion of latent MMP-2 was noted. However, the intracellular localization of the immunoreactive protein for MMP-2 was altered in response to paclitaxel treatment. Interestingly, paclitaxel increased the appearance of TIMP-2 protein in culture medium (P = 0.002) but did not change the expression of mRNA for TIMP-2 in Ovcar-3 cells. These data show that paclitaxel is an effective suppressor of Ovcar-3 cell invasion. It inhibits attachment and migratory activities of the cells but also causes a release of TIMP-2 protein into the tissue culture medium.
Westerlund
A
A
Department of Oncology and Radiotherapy, University Hospital of Oulu, Finland.
Hujanen
E
E
Höyhtyä
M
M
Puistola
U
U
Turpeenniemi-Hujanen
T
T
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D018093:Gelatinases / Q000032:analysis / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis; D008870:Microtubules / Q000187:drug effects; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D017239:Paclitaxel