Journal Search Engine
Search Advanced Search Adode Reader(link)
Download PDF Export Citaion korean bibliography PMC previewer
ISSN : 1225-1577(Print)
ISSN : 2384-0900(Online)
The Korean Journal of Oral and Maxillofacial Pathology Vol.42 No.3 pp.49-57

CXCR7-knockdown by Small Interfering RNA Inhibits Proliferation and Migration of Oral Squamous Cell Carcinoma Cells

Ji-Soo Hong, Ji-Yeon Kim, Seong-Doo Hong, Jae-Il Lee*
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea
Correspondence: Jae-IL Lee, Department of oral pathology, School of Dentistry and Dental Research Institute, Seoul National University, 28 Yeongeon-dong, Jongno-gu, Seoul 110-749, Republic of Korea Tel: +82-2-740-8648, Fax: +82-2-764-6088 E-mail:
June 1, 2018 June 8, 2018 June 22, 2018


The role of CXCR7, a seven-transmembrane G-protein coupled chemokine receptor, which binds with high affinity to chemokine CXCL11 and CXCL12 in oral cancer cells and the effect of transient CXCR7-downregulation on proliferation and migration of oral squamous cell carcinoma (OSCC) cells have not been reported. The aim of the present study was to evaluate the effects of CXCR7 on an OSCC cell line. In this study, we down-regulated CXCR7 in the KOSCC25B OSCC cell line by siRNA. In vitro cell proliferation and migration assays were used to investigate the effect of CXCR7- downregulation on cell proliferation and migration in si.KOSCC25B cells. The CXCR7 down-regulated OSCC cells grew significantly slower than the negative control siRNA transfected KOSCC25B cells (p<0.05). Additionally, migration of si.KOSCC25B cells decreased significantly compared with non-transfected KOSCC25B cells (p<0.007). These results suggest that down-regulation of CXCR7 induces anti-proliferative and anti-migratory effects in OSCC, and that CXCR7 may be a useful target molecule for the treatment of OSCC.

구강편평세포암종의 증식능과 이주능에 영향을 미치는 CXCR7의 역할

홍 지수, 김 지연, 홍 성두, 이 재일*
서울대학교 치의학대학원 구강병리학교실



    Patients with oral squamous cell carcinomas (OSCCs) that have spread to the regional lymph nodes have a poor 5-year survival rate compared with patients without metastasis [1]. The spread to regional lymph nodes in the neck2), which can occur soon after the development of OSCC, is facilitated by rich lymphatic drainage from of the oral cavity [3]. A number of molecules have been implicated in the metastasis of OSCC4),5).

    Chemokines are small soluble molecules (8 – 14kDa) secreted by different types of cells, which can mediated the directional movement of cells and chemotaxis by binding to G-protein coupled seven-span transmembrane receptors (GPCRs) on the plasma membrane of target cells6). Also, binding of chemokines to their receptors causes attraction of different types of blood leukocytes to sites of infection and inflammation7).

    At present, more than 50 chemokines and 20 chemokine receptors have been found. Among these chemokines and their receptors, the stromal cell-derived factor 1 (SDF-1 also called CXCL12) / CXCR4 axis has been demonstrated to be involved in the lymph node or distant metastasis of several types of cancer, including prostate cancer8), kidney cancer 9), neuroblastoma10), breast cancer6), and melanoma11). In addition, our previous studies have demonstrated that among OSCC patient tissue samples, a CXCR4-positive group demonstrated significantly higher PCNA LI than did the CXCR4-negative group12).

    Chemokines usually bind to multiple receptors and the same receptor may bind more than one chemokine. However, one exception to this rule has been accepted for many years ; the SDF-1 binds exclusively to CXCR4, and has CXCR4 as its only receptor13),14). However, several reports recently provided evidence that SDF-1 also binds to another seven-transmembrane span receptor called CXCR7, sharing this receptor with another chemokine family member called interferon-inducible T-cell chemoattractant (I-TAC)15),16). This finding broke the long-standing assumption that CXCR4 was the only receptor specific to SDF-1. Therefore, downstream cell function, which has been previously attributed to CXCR4, may also result from a CXCR7-mediated effect.

    Over the past several years, it has been found that CXCR7 signaling promotes cancer cell survival through an antiapoptotic mechanism17),18).

    Miao et al., have demonstrated that expression of CXCR7 on breast and lung cancer cells positively correlates with their proliferation, vascularization, and metastatic potential. While CXCR7-transduced murine human breast or lung cancer cell lines grow larger tumors in immunodeficient mice, down-regulation of CXCR7 expression by siRNA resulted in formation of smaller tumors. CXCR7 overexpressing breast cancer cells also showed higher seeding efficiency in murine lungs in vivo19). In another study, CXCR7 was found to be highly expressed on human prostate cancer cells. According to this study, CXCR7 regulates cell proliferation most likely because of enhanced cell survival, adhesion, and chemotaxis20).

    Thus similarly to CXCR4, CXCR7 may promote expansion and metastasis of certain tumor types and could be a potential prognostic factor and a target for developing new anti-cancer and anti-metastatic drugs.

    However, there have been no reports on the effect of transient down-regulation of CXCR7 by siRNA in oral cancer cells. And further, research is needed to evaluate the role of CXCR7 in OSCC cells. In the current study, we investigated the effects of CXCR7-downregulation on in vitro proliferation and migration of OSCC cells.


    This study primarily made use of a published cell line (obtained from Dr. Lee’s Laboratory21) and is exempt from assessment by Institutional Review Board of Seoul National University School of Dentistry.


    SCC-4, SCC-9, SCC-15 and SCC-25 human OSCC cells, purchased from American Tissue Cell Collection (Manassas, VA, USA) were cultured in DMEM:F12 mixture. HSC-2, HSC-3, HSC-4, Ca9-22, HO-1-N-1 and HO-1-U-1 cell lines, purchased from Japanese Collection of Research Bioresources Cell Bank were cultured in RPMI 1640. KOSCC-11, KOSCC-25B, and KOSCC-33A human OSCC cells established from tumors obtained from Korean cancer patients, and named Korean oral squamous cell carcinoma cell line (KOSCC), were cultured in DMEM.

    These 13 cell lines were cultured in media supplemented with 10% fetal bovine serum (FBS; Gibco, Carlsbad, CA, USA), 1% antibiotics antimycotic solution (100 U/ml penicillin and 100 ㎍/ml streptomycin; Gibco). The cell cultures were maintained at 37℃ in a humidified atmosphere of 95% air and 5% CO2.


    KOSCC25B cells were cultured in a 6-well plate (1 × 106 cells per well) in 10% FBS containing medium. After overnight incubation, cells were transfected with Hs_CMKOR1_6 Flexitube siRNA (Qiagen, Hilden, Germany) at a concentration of 50nM, using Hiperfect transfection reagent (6 ㎕/ml, Qiagen) according to the manufacturer’s instructions. Transfected cells were named si.KOSCC25B. And negative control siRNA transfected KOSCC25B cells were used as control.


    After 24, 48, and 72h of transfection, we evaluated CXCR7 down-regulation by semi-quantitative PCR analysis.

    The mRNA was purified from the cells using Trizol reagent (Invitrogen, Calsbad, CA, USA) according to the manufacturer’s recommended protocol. Two micrograms of RNA was converted into cDNA using random primers and reverse transcriptase. cDNA was PCR amplified in 30 cycles each consisting of 94℃ for 30 s, 60℃ for 50 s, 72℃ for 50 s. The primer pairs for CXCR7 and GAPDH were as follows ; CXCR7 forward, 5”- AAG AAG ATG GTA CGC CGT GTC GTC TGC ATC CTG –3’ ; CXCR7 reverse, 5”–CTG CTG TGC TTC TCC TGG TCA CTG GAC GCC GAG -3”; GAPDH forward, 5”- GAA GGT GAA GGT CGG AGT C-3”; GAPDH reverse, 5”- CAA AGT TGT CAT GGA TGA CC -3”.

    PCR products were electrophoresed on 1.5% agarose gel containing ethidium bromide and visualized by UV-induced fluorescence.


    To determine the proliferation rate, KOSCC25B cells were seeded on 12-well plates (BD Falcon, Franklin Lakes, NJ, USA) at 3 × 104 cells per well in DMEM with or without 10% FBS. After overnight of incubation, the si.CXCR7 cells were transfected with CXCR7 siRNA or si.Con cells were transfected with negative control siRNA.

    And then, after 1, 2, and 3days the cells were trypsinized and stained with 0.4% Trypan Blue (Gibco). The total cell number and the proportion of dead cells were counted by hemocytometer. Cell death was determined by the presence of cytoplasmic Trypan Blue. This assay was performed in triplicate in each experiment, and each experiment was repeated three times.


    A total of 1 × 105 KOSCC25B cells were seeded in the upper compartment (8 μm pore size) in DMEM medium with or without 10% FBS. After overnight incubation, si.CXCR7 cells or si.Con cells were transfected using CXCR7 siRNA or negative control si.RNA as above.

    Then, after 24, 48h incubation, the cells on the upper surface of the filter were wiped off with a cotton swab, and the remaining cells were stained with the Diff-Quick stain set (Sysmex, Kobe, Japan). Using a microscope at × 100 magnification, migration was quantified by counting the number of cells that migrated through the pores to the lower side of the filter. This assay was performed in triplicate in each experiment, and each experiment was repeated 3 times.


    Statistical significance was determined by unpaired Student’s t test with a threshold of P < 0.05. The correlation coefficient was calculated by using SPSS 12.0.



    We screened 13 OSCC cell lines in order to obtain a cell line with high expression cell line of CXCR7. Of these 13 cell lines, SCC4, HSC-2, KOSCC11 and KOSCC33A showed markedly low CXCR7 levels as detected by semi-quantitative PCR analysis. Except for these 4 cell lines, the cell lines showed high CXCR7 expression levels (Fig.1).

    Thus, of the KOSCC cell line series, the only cell line with high level expression was KOSCC25B, this cell line was chosen for the present study.


    We assessed siRNA mediated CXCR7 down-regulation by semi-quantitative PCR analysis. As shown in Fig. 2A, CXCR7 mRNA levels were reduced in si.KOSCC25B cells, as compared with siRNA control transfected KOSCC25B cells. The CXCR7 mRNA level had decreased by 48h after transfection with siRNA. At 72h after transfection, the CXCR7 mRNA level had recovered. GAPDH was used as an internal control to monitor whether RNA isolation and RT-PCR were reliable. As shown in Fig. 2B, GAPDH was detected in both transfected and siRNA control transfected samples, as expected.

    Therefore, CXCR7 expression was down-regulated at the mRNA level in si.KOSCC25B cells in the first 48h.


    To determine the effect of CXCR7 down-regulation on proliferation of si.KOSCC-25B, the cell numbers were counted by hemocytometer. In serum-free media condition, si.KOSCC25B cells proliferated at 88.21%, 73.03% and 75.38% at 1, 2, and 3 days after transfection, respectively, compared with control. Additionally, in the presence of 10% FBS, si.KOSCC25B cells proliferated at 82.34%, 68.97%, and 55.45% at 1, 2 and 3days after transfection, respectively (P < 0.05). Thus, we established that si.KOSCC25B cells grew significantly slower than the siRNA control transfected KOSCC-25B cells (Fig 3).

    These data indicated that the down-regulation of CXCR7 has an anti-proliferative effect on OSCC cells.


    Due to the important role of the CXCR7/SDF-1 axis in cancer metastasis, we investigated whether CXCR7-downregulation decreased migration of OSCC cells. As shown in Fig. 4, CXCR7 down-regulation decreased KOSCC25B cell migration. At 24 h and 48 h after siRNA transfection, si.KOSCC25B decreased to 73% and 64%, compared to siRNA control transfected cells, respectively, in serum-starved media (P < 0.000). In the presence of 10% FBS, si.KOCC25B migration decreased to 35% and 22% at 24 h and 48 h, respectively, compared to the control cells (P < 0.003).

    Therefore, these data indicated that the down-regulation of CXCR7 decreased migration both in the presence and absence of FBS.


    It is well-known that chemokines interact with GPCRs to activate down-stream signaling pathways that enhance cancer cell growth, migratory behavior, and cell survival [22, 23], however, the role of the chemokine receptor, CXCR7, in cancer has not been elucidated fully. In this study, we show that CXCR7 is involved in the proliferation and migration of OSCC cells.

    SDF-1 is a member of the CXC subfamily of chemokines and is expressed in a variety of tissues, including lung, liver, bone marrow and lymph nodes24)-26). SDF-1 exerts its functions through binding to its receptor, CXCR4, which is present on the cell surface and is a seven-transmembrane span GPCR27). SDF-1 plays a role in a number of important physiological processes, including leukocyte trafficking and vasculogenesis25),28). More importantly, SDF-1 plays a crucial role in the process of invasion and metastasis of tumor cells 29). SDF-1 stimulates proliferation, dissociation, migration, and invasion in a wide variety of tumor cells, including breast cancer cells, pancreatic cancer cells and HCC cells 29),30),31). Moreover, expression of the SDF-1 receptor, CXCR4, in clinical samples is associated with lymph node metastasis of OSCC32),33).

    A recent study has shown that chemokine receptor CXCR7 can also bind to SDF-1, and it has thus been identified as a second receptor for SDF-115). CXCR7 is expressed in many different tissues, including neurons, immune cells, and endothelial cells; receptor-mediated signaling can occur by binding either of its 2 known ligands, CXCL11 or CXCL1234)-37).

    Similar to what is known about CXCR4, recent reports have indicated that CXCR7 promotes cancer cell survival through anti-apoptotic mechanisms34),38). Therefore, downstream cell functions, which have been previously attributed to CXCR4 may also result from CXCR7-mediated signaling. In the present study, we investigated the effect of CXCR7-down-regulation on cell proliferation and migration. Down-regulation of CXCR7 induced anti-proliferative and anti-migration effects in KOSCC25B cells. To our knowledge, this the first description of siRNA mediated CXCR7-knockdown in oral cancer cells.

    Recent studies in breast cancer cells indicated that downregulation of CXCR4 by siRNA inhibits invasion in vitro39) and metastasis and growth in vivo40),41). In addition, we previously investigated CXCR4 signaling in oral cancer cells and observed effects on cell proliferation, migration, and invasion13).

    Thus, it was plausible that, similar to CXCR4, CXCR7 may promote proliferation and migration of OSCC cells. Our results support this proposal, and indicate that CXCR7 could be both a potential prognostic factor and a target for developing new anti-cancer and anti-metastatic drugs.



    Screening of OSCC cell lines for CXCR7 expression by semi-quantitative PCR analysis.

    (A) RT-PCR was performed for CXCR7 mRNA expression in established human oral cancer cell lines.

    (B) GAPDH was used as a control.


    Confirmation of CXCR7 down-regulated by siRNA. KOSCC25B cells were transfected with 50nM CXCR7 for 24hours, 48hours and 72hours. si.RNA negative control transfected KOSCC25B cells use control. (B) GAPDH was used as a loading control.


    Anti-proliferative effects of CXCR7 down-regulation.

    Cell prolifration assay showed that the CXCR7 down-regulation KOSCC25B cells grew signficantly slower than negative control siRNA transfected KOSCC25B cells. (A) Without FBS. si.KOSCC25B cells proliferated at 88.21%, 73.03% and 75.38% at 1day, 2day and 3day respectively, of the rate of si.RNA control transfected KOSCC25B cells in without FBS condition. (B) With FBS. In with 10% FBS media, si.KOSCC25B cells proliferated 82.34%, 68.97% and 55.45% at 1day, 2ay and 3day respectively (* = P < 0.05, ** = P < 0.01).


    Reduced migration due to CXCR7 down-regulation.

    si.KOSCC25B cells showed reduced migration. The migration of si.KOSCC25B decreased to 73% and 64% at 24hours and 48hours in without FBS condition. In with 10% FBS condition, si.KOCC25B decreased to 35% and 22% at 24hours and 48hours compared with negative control si.RNA transfected cells (* = P < 0.003, ** = P < 0.000).



    1. R.T. Greenlee , T. Murray , S. Bolden (2000) Cancer statistics., CA Cancer J. Clin., Vol.50 ; pp.7-33
    2. S.K. Mukherji , D. Armao , V.M. Joshi (2001) Cervical nodal metastases in squmous cell carcinoma of the head and neck : what to expect., Head Neck, Vol.23 ; pp.995-1005
    3. R. Ossoff , G. Sisson (1981) Lymphatics of the floor of the mouth and neck : anatomical studies related to contralateral drainage pathways., Laryngoscope, Vol.91 ; pp.1847-1850
    4. R.P. Takes , R.J. Baatenburg de Jong , M. Alles (2002) Markers for nodal metastasis in head and neck squmous cell cancer., Arch. Otolaryngol. Head Neck Surg., Vol.128 ; pp.512-518
    5. C.E. Schmalbach , D.B. Chepeha , T.J. Giordano (2004) Molecular profiling and the identification of genes associated with metastatic oral cavity pharynx squamous cell carcinoma., Arch. Otolaryngol. Head Neck Surg., Vol.130 ; pp.295-302
    6. A. Rot , U.H. Von Andrian (2004) Chemokines in innate adaptive host defense : basic chemokinese grammar for immune cells., Annu. Rev. Immunol., Vol.22 ; pp.891-928
    7. D. Rossi , A. Zlotnik (2000) The biology of chemokines and their receptors., Annu. Rev. Immunol., Vol.18 ; pp.217-242
    8. I. Bennett , P. Cronholm , A. Ochroch (2002) Use of the strom alcell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone., J. Urol., Vol.168 ; pp.203-204
    9. A.J. Schrader , O. Lechner , M. Templin (2002) CXCR4/CXCL12 expression and signaling in kidney cancer., Br. J. Cancer, Vol.86 ; pp.1250-1256
    10. H. Geminder , O. Sgi-Assif , L. Goldberg (2001) A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma., J. Immunol., Vol.167 ; pp.4747-4757
    11. T. Murakami , W. Maki , A.R. Cardones (2002) Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells., Cancer Res., Vol.62 ; pp.7328-7334
    12. J.S. Hong , H.K. Pai , K.O. Hong (2009) CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells., J. Oral Pathol. Med., Vol.382 ; pp.214-219
    13. T. Nagasawa , S. Hirota , K. Tachibana (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC Chemokine PBSF/SDF-1., Nature, Vol.382 ; pp.635-638
    14. Q. Ma , D. Jones , T.A. Springer (1999) The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment., Immunity, Vol.56 (10) ; pp.463-471
    15. F. Libert , A. Parmentier , A. Lefort (1990) Complete nucleotide sequence of a putative G protein coupled receptor : RDC1., Nucleic Acids Res., Vol.18 ; pp.1917
    16. N.M. Law , S.A. Rosenzweig (1994) Characterization of the G-protein linked orphan receptor GPRN1/RDC1., Biochem. Biophys. Res. Commun., Vol.201 ; pp.58-65
    17. J. Burns , B. Summers , Y. Wang (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development., J. Exp. Med., Vol.203 ; pp.2201-2213
    18. K. Hattermann , J. Held-Feindt , R. Lucisu (2010) The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects., Cancer Res., Vol.70 ; pp.3299-3308
    19. Z. Miao , K.E. Luker , B.C. Summers (2007) CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature., Proc. Natl. Acad. Sci. USA, Vol.104 ; pp.15735-15740
    20. J. Wang , Y. Shiozawa , J. Wang (2008) The role of CXCR7/ RDC1 as a chemokine receptor for CXCL12/SDF1 in prostate cancer., J. Biol. Chem., Vol.88 ; pp.279-289
    21. G. Lee , Y.B. Kim , J.H. Kim (2002) Characterization of novel cell lines established from three human oral squamous cell carcinomas., Int. J. Oncol., Vol.20 ; pp.1151-1159
    22. F. Balkwill (2004) Cancer and chemokine network., Nat. Rev. Cancer, Vol.4 ; pp.540-550
    23. M. Ratajczak , E. Zuba-Suma , M. Kucia (2006) The pleiotropic effects of the SDF-1CXCR4 axis in organogenesis regeration and tumorigenesis., Leukemia, Vol.20 ; pp.1915-1924
    24. J.L. Pablos , A. Amara , A. Bouloc (1999) Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin., Am. J. Pathol., Vol.155 ; pp.1577-1586
    25. A. Aiuti , I.J. Webb , C. Bleul (1997) The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a New mechanism to explain the mobilization of CD34+ progenitors to peripheral blood., J. Exp. Med., Vol.185 ; pp.111-120
    26. K. Tashiro , H. Tada , R. Heilker (1993) Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins., Science, Vol.261 ; pp.600-603
    27. P.M. Murphy (1994) The molecular biology of leukocyte chemoattractant receptors., Annu. Rev. Immunol., Vol.12 ; pp.593-633
    28. T. Nagasawa , S. Hirota , K. Tachibana (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1., Nature, Vol.382 ; pp.635-638
    29. A. Muller , B. Hmey , H. Soto (2001) Involvement of chemokine receptors in breast cancer metastasis., Nature, Vol.410 ; pp.50-56
    30. F. Marchesi , P. Monti , B.E. Leone (2004) Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4., Cancer Res., Vol.64 ; pp.8420-8427
    31. A. Sutton , V. Friand , S. Brule-Donneger (2007) Stromal cell-derived factor-1/Chemokine (C-X ?"C Motif) ligand 12 stimulates human hepatoma cell growth, migration, and invasion., Mol. Cancer Res., Vol.5 ; pp.21-33
    32. A. Almofti , D. Uchida , N.M. Begum (2004) The clinicopathological significance of the expression of CXCR4 protein in oral squamous cell carcinoma., Int. J. Oncol., Vol.25 ; pp.65-71
    33. T. Ishikawa , K. Nakashiro , S. Hara (2006) CXCR4 expression is associated with lymph node metastasis of oral squamous cell carcinoma., Int. J. Oncol., Vol.28 ; pp.61-66
    34. J. Burns , B. Summers , Y. Wang (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development., J. Exp. Med., Vol.203 ; pp.2201-2213
    35. Z. Miao , K. Luker , B. Summers (2007) CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor associated vasculature., Proc. Natl. Acad. Sci. USA, Vol.104 ; pp.15735-15740
    36. Y. Wang , G. Li , A. Stanco (2011) CXCR4 and CXCR7 have distinct functions in regulating interneuron migration., Neuron, Vol.69 ; pp.61-76
    37. S. Infantino , B. Moepps , M. Thelen (2006) Expression and regulation of the orphan receptor RDC1 and its putative ligand in human dendritic and B cells., J. Immunol., Vol.176 ; pp.2197-2207
    38. R. Mentlein (2010) The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects., Cancer Res., Vol.70 ; pp.3299-3308
    39. Y. Chen , G. Stamatoyannopoulos , C.Z. Song (2003) Downregulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro., Cancer Res., Vol.63 ; pp.4801-4804
    40. M.C. Smith , K.E. Luker , J.R. Garbow (2004) CXCR4 regulates growth of both primary and metastatic breast cancer., Cancer Res., Vol.64 ; pp.8604-8612
    41. N. Lapteva , A.G. Yang , D.E. Sanders (2005) CXCR4 knockdown by small interfering RNA abrogates breast tumor growth in vivo., Cancer Gene Ther., Vol.12 ; pp.84-89
    오늘하루 팝업창 안보기 닫기