Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells.
Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) display variations in invasive and metastatic behavior. We aimed to clarify the mechanism(s) underlying this observation and transfected vectors carrying CD147, a glycoprotein enriched on the surface of tumor cells that stimulates the production of matrix metalloproteinases (MMPs), and specific shCD147 into MCF7 and MCF7/Adr cells, respectively. Using quantitative real-time polymerase chain reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up-regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which promoted tumor cells metastasis and conferred them multidrug resistance to P-gp substrate drugs, as determined by in vitro invasion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. On the other hand, silencing of CD147 in MCF7/Adr cells led to the opposite effect. Moreover, Erk1/2 in CD147-overexpressing clones were observed to be highly activate and after treatment with U0126, an Erk1/2-specific inhibitor, the expression of MDR1, MMP2 and MMP9 were decreased significantly. Thus, CD147 may assume a dual role, since it had intrinsic stimulative effects on tumor invasion in vitro as well as increasing resistance to P-gp substrate drugs.
Li
Qing-Quan
QQ
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wang
Wen-Juan
WJ
Xu
Jing-Da
JD
Cao
Xi-Xi
XX
Chen
Qi
Q
Yang
Jin-Ming
JM
Xu
Zu-De
ZD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D000970:Antineoplastic Agents / Q000633:toxicity; D051926:Basigin / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017931:DNA Primers; D018432:Drug Resistance, Multiple; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051926:Basigin; D020782:Matrix Metalloproteinases