Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression.
BACKGROUND
The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP).


METHODS
We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC(50)) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined.


RESULTS
CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC(50)) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression.


CONCLUSIONS
Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.
Hao
J
J
Faculty of Medicine, UNSW, Kensington NSW 2052, Australia.
Chen
H
H
Madigan
M C
MC
Cozzi
P J
PJ
Beretov
J
J
Xiao
W
W
Delprado
W J
WJ
Russell
P J
PJ
Li
Y
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D051926:Basigin / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use; D015854:Up-Regulation
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D027501:Monocarboxylic Acid Transporters; D043823:Taxoids; D051926:Basigin; D000077143:Docetaxel