CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells.
BACKGROUND
Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells.


METHODS
We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples.


RESULTS
CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells (P < 0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells (P < 0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.


CONCLUSIONS
These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.
Hong
Ji-Soo
JS
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
Pai
Hyun-Kyung
HK
Hong
Kyoung-Ok
KO
Kim
Mi-Ae
MA
Kim
Ji-Hong
JH
Lee
Jae-Il
JI
Hong
Sam-Pyo
SP
Hong
Seong-Doo
SD
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002999:Clone Cells; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D008207:Lymphatic Metastasis / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D034741:RNA, Small Interfering / Q000502:physiology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C527276:CXCR4 protein, human; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4