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Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

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Abstract

Cancer metastasis and anti-cancer drug resistance are the major reason for the failure of clinical cancer treatment. We evaluated CD147, monocarboxylate transporters (MCT1 and MCT4), and multidrug resistance (MDR) markers (MDR1 and MRP2) in 4 epithelial ovarian cancer (EOC) cell lines and primary tumors (n = 120) along with the matched metastatic lesions (n = 40) with immunofluorescence labeling. We correlated CD147 with MCT1, MCT4, MDR1 and MRP2 markers in primary and metastatic cells in cell lines and tissues using confocal microscopy. We also investigated the relationship of expression of CD147, MCT1 and MCT4 with various progression parameters. Our results indicate that the co-expression of CD147 with MCTs or MDR markers was found in primary and metastatic EOC cells and stromal cells; the over-expression of CD147, MCT1 and MCT4 was found in most primary and the matched metastatic lesions of EOC, and was significantly associated with tumor stage, grade, residual disease status and presence of ascites (P < 0.05) but not with histology type (P > 0.05). These results suggest that over-expression of CD147, MCT1 and MCT4 is correlated with EOC progression, and co-expression of CD147 and MCT1/MCT4 is related to drug resistance during EOC metastasis and could be useful therapeutic targets to prevent the development of incurable, recurrent and drug resistance EOC.

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Abbreviations

ABC:

ATP-binding cassette

CT:

Computed tomography

EOC:

Epithelial ovarian cancer

FBS:

Fetal bovine serum

HEG:

High-expression group

LEG:

Low-expression group

MAb:

Monoclonal antibody

MCTs:

Monocarboxylate transporters

MDR:

Multidrug resistance

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

PAb:

Polyclonal antibody

Pgp:

P-glycoprotein

RNAi:

RNA interference

siRNA:

Small interfering RNA

shRNA:

Short hairpin RNA

TBS:

Tris buffered saline

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Acknowledgements

We thank Dr. QingKai Yu (Pathologist, Director of Department of Pathology, Henan Cancer Hospital, China) who assisted with the diagnosis of EOC. We also thank Dr John Allen (Centenary Institute, University of Sydney, Australia) for kindly providing an MDR1 positive control cell line. This study was partially funded by an international collaborative grant from Henan Health Board, China (HC and LW) as well as Career Development Fellowship from Cancer Institute NSW Australia (YL).

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Henan Cancer Hospital, 127 Dongming Rd., Zhengzhou, Henan, 450008, China

    Hongmin Chen & Li Wang

  2. Faculty of Medicine, University of New South Wales, Kensington, Sydney, NSW, 2052, Australia

    Hongmin Chen, Li Wang, Julia Beretov, Jingli Hao, Weiwei Xiao & Yong Li

  3. Anatomical Pathology, St George Hospital, Sydney, NSW, 2217, Australia

    Julia Beretov

  4. Cancer Care Centre, St George Hospital, Gray St, Kogarah, Sydney, NSW, 2217, Australia

    Julia Beretov, Jingli Hao, Weiwei Xiao & Yong Li

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  1. Hongmin Chen
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  2. Li Wang
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Correspondence to Li Wang or Yong Li.

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Chen, H., Wang, L., Beretov, J. et al. Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression. Clin Exp Metastasis 27, 557–569 (2010). https://doi.org/10.1007/s10585-010-9345-9

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