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. 2009 Aug 4;101(3):432-40.
doi: 10.1038/sj.bjc.6605185. Epub 2009 Jul 14.

Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

H Chen  1 , J Hao, L Wang, Y Li
Affiliations

Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

H Chen et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
Coimmunolabelling of uPA, CD44, MDR1 and MRP2 in EOC. Representative confocal images of uPA and MDR1 (red; Alexa-594), and CD44 and MRP2 (green; Alexa-488) expression in EOC primary and metastatic cell lines are shown. Merged images, and red and green channels are shown separately. (A) uPA expression; (B) CD44 expression; (C) MDR1 expression; (D) MRP2 expression; (E) Colocalisation of uPA with CD44; (F) Colocalisation of uPA with MRP2; (G) Colocalisation of CD44 with MDR1. Magnification: A–G × 400.
Figure 2
Figure 2
Coimmunolabelling of uPA, CD44, MDR1 and MRP2 in EOC. Representative confocal images of uPA and MRP2 (green; Alexa-488), and CD44 and MDR1 (red; Alexa-594) expression in EOC primary and metastatic cell lines are shown. Merged images, and red and green channels are shown separately. (A) uPA expression; (B) CD44 expression; (C) MDR1 expression; (D) MRP2 expression; (E) Colocalisation of uPA with MDR1; (F) Colocalisation of CD44 with MRP2; (G) IgG-negative control. Magnification: A–G × 400.
Figure 3
Figure 3
Immunofluoresence staining for uPA, CD44 and MDR1 in primary and metastatic EOCs. Representative images from different patients. Representative confocal images of uPA and CD44 (green; Alexa-488) and MDR1 (red; Alexa-594) expression in EOC primary and metastatic EOC tissues are shown. Low levels of uPA, CD44 and MDR1 are shown in primary EOC tissues (A–C), respectively. Medium levels of uPA, CD44 and MDR1 are shown in primary EOC tissues (D–F), respectively. High levels of uPA, CD44 and MDR1 are shown in metastatic EOC tissues (G–I), respectively. uPA immunolabelling is homogeneous and is generally seen on epithelial and stromal cells. Magnification: A–I × 400.
Figure 4
Figure 4
Coimmunolabelling of uPA, CD44 and MDR1 in EOC tissues. Representative confocal images of uPA (red; Alexa-594 or green; Alexa-488), CD44 (green; Alexa-488) and MDR1 (red; Alexa-594) expression in EOC primary tumours and matched metastatic lesions are shown. Merged images and red and green channels are shown separately. (A) Colocalisation of uPA with CD44 in primary EOC tissues; (B) Colocalisation of uPA with CD44 in metastatic EOC tissues; (C) Colocalisation of uPA with MDR1 in primary EOC tissues; (D) Colocalisation of uPA with MDR1 in metastatic EOC tissues; (E) Colocalisation of CD44 with MDR1 in primary EOC tissues; (F) Colocalisation of CD44 with MDR1 in metastatic EOC tissues. uPA immunolabelling is homogeneous and is generally seen on epithelial and stromal cells. Magnification: A–F × 400.
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