Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression.
BACKGROUND
Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of treatment failure and mortality in cancer patients.


METHODS
We evaluated invasive markers of urokinase plasminogen activator (uPA) and CD44 and multiple drug-resistance (MDR) markers of MDR1 and MRP2 in four epithelial ovarian cancer (EOC) cell lines, primary tumours (n=120) and matched metastatic lesions (n=40) by immunofluoresence labelling. We correlated uPA and CD44 with MDR markers in primary and metastatic cells using confocal microscope. We also investigated the relationship of the expression of uPA, CD44 and MDR1 with various progression parameters.


RESULTS
The coexpression of uPA and CD44 with MDR markers was found in primary and metastatic cells. The overexpression of uPA, CD44 and MDR1 was found in most primary and matched metastatic lesions of EOC, and was significantly associated with tumour stage, grade, residual disease status, relapse and presence of ascites (P<0.05), but not with histology type (P>0.05).


CONCLUSIONS
Our results suggest that the overexpression of uPA, CD44 and MRD1 is correlated with EOC progression; both uPA and CD44 are related with drug resistance during EOC metastasis and could be useful therapeutically.
Chen
H
H
Department of Gynecologic Oncology, Henan Tumour Hospital, 127 Dongming Rd, Zhengzhou, Henan 450008, China.
Hao
J
J
Wang
L
L
Li
Y
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D018613:Microscopy, Confocal; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018960:Hyaluronan Receptors; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014568:Urokinase-Type Plasminogen Activator; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human