Expression of CCL5 and S100A4 protein in breast cancer tissues and their relationship with clinicopathological features and prognosis / 中国基层医药

Objective To investigate the relationship between the expression of CC chemokine ligand 5(CCL5)and S100 calcium binding protein A4 (S100A4)protein in breast cancer tissues with clinicopathological features and prognosis.Methods The expression of CCL5 and S100A4 in 40 cases of normal breast tissues and 120 cases of breast cancer were detected by immunohistochemistry,and the relationship between the degree of expres-sion and the clinicopathological features and prognosis of breast cancer was analyzed.Results The expression posi-tive rates of CCL5 and S100A4 in breast cancer tissues were 56.67% and 62.50% respectively,which were not expressed in normal breast tissues,and the differences were statistically significant (χ2CCL5 =39.403,P 0.05 ).And the expression of S100A4 was statistically correlated with clinical staging(χ2 =44.311,P 0.05).The expression of CCL5 and S100A4 in breast cancer was positively correlated(r =0.301, P <0.01).CCL5 was positively correlated with the recurrence of breast cancer(OR =6.270,P <0.01),and S100A4 was not correlated with the recurrence of breast cancer(OR =1.103,P =0.768).Survival analysis showed that the disease -free survival time of patients with positive CCL5 expression was significantly shorter than the patients with negative CCL5 expression(χ2 =11.851,P <0.01 ),and the disease -free survival time of patients with positive S100A4 expression was significantly shorter than the patients with negative S100A4 expression(χ2 =5.433,P =0.021).The joint detection showed that the disease -free survival time in CCL5(+)+S100A4(+)group was sig-nificantly lower than that of CCL5(+)or S100A4(+)group(χ2 =15.341,P <0.01)and CCL5 (-)+S100A4 (-)group(χ2 =15.341,P <0.01).Conclusion The expression of CCL5 and S100A4 in breast cancer can reflect the metastasis and staging of breast cancer,which can be used to judge the clinical pathological characteristics and prognosis of breast cancer.

Overexpression of amphiregulin promotes the growth of mouse colon carcinoma CT26 cells in vivo / 肿瘤

Objective: To investigate the effect of epidermal growth factoramphiregulin (AREG) on the growth of mouse colon carcinoma CT26cells and its related mechanisms.Methods: The protein expression level of AREG in different mouse cancer cells was detected by ELISA. Mouse colon carcinoma CT26 cells, melanoma B16 cellsand hepatocellular carcinoma LPC-Akt cells were transfected with the recombinant lentiviralplasmid carrying AREG gene, while the ones transfected with empty plasmid were used asthe negative controls. After AREG overexpression, the cell proliferation, colony-formingabilities and cell cycle progression in vitro were detected by MTT, colony-forming assay andFCM, respectively. After the homograft mouse model of CT26 cells was constructed, thegrowth of homograft tumor was observed, the distribution of immune cells in tumor tissueswas detected by FCM, furthermore the expression of chemokine was detected by real-timefluorescent quantitative PCR.Results: The levels of AREG expression were relatively low in mouse colon carcinoma CT26cells, melanoma B16 cells and hepatoma LPC-Akt cells. AREG overexpression did notmarkedly affect the proliferation, colony-forming abilities and cell cycle progression of thesethree types of tumor cells in vitro (all P > 0.05). However, in the homograft mouse model ofCT26 cells, AREG overexpression significantly promoted the growth of tumor cells in vivo (P <0.01), decreased the percentage of CD8+ T cells (P < 0.05), and reduced the mRNA level ofCC chemokine 5 ligand (CCL5) (P < 0.05) which was related to CD8+ T cell recruitment.Conclusion: AREG promotes the growth of mouse colon carcinoma CT26 cells in vivo . AREGmay affect the tumor microenvironment by regulating the production of chemokine which isrelated to CD8+ T cell recruitment.

Relationship between the expression of chemokines and their receptors in the maternal-fetal ;interface and pathogenesis of unexplained recurrent spontaneous abortion / 中华妇产科杂志

Objective To explore the relationship between the expression of chemokines and their receptors in the maternal-fetal interface and the pathogenesis of unexplained recurrent spontaneous abortion (URSA). Methods 8-10 weeks CBA/J female mice were mated with DBA/2 and BALB/c male mice at the ratio of 2∶1 to establish the model of normal pregnant mice (CBA/J × BALB/c) and URSA mice (CBA/J × DBA/2). Sixty mice were divided into 6 groups, with ten in each group. The mice in the normal unpregnancy group were executed for endometrial tissues; the mice in the embryonic implantation normal pregnancy group were executed for endometrial tissues at the sixth day of gestation; the mice in the embryonic development normal pregnancy group were executed for decidua and chorionic tissues at the fourteenth day of gestation. While, the mice in the embryonic implantation URSA group were executed for endometrial tissues at the sixth day of gestation;the mice in the pre-abortion URSA group were executed for decidua and chorionic tissues at the ninth day of gestation;the mice in the post-abortion URSA group were executed for decidua and chorionic tissues at the fourteenth day of gestation. The chemokines and their receptors in different tissues of the mice were determined by western blot, including the protein expression of stromal cell derived factor (CXCL12), monocyte chemotactic protein 1 (CCL2), regulated upon activation normal T cell expressed and secreted(RANTES) and their receptor CXCR4, CCR2, CCR5 in maternal-fetal interface. Results (1) The protein expression of CXCL12 and CXCR4, CCL2 and CCR2, RANTES and CCR5 in endometrial tissues of the normal unpregnant group were 0.13±0.04 and 0.18±0.09, 0.057±0.023 and 0.39± 0.08, 0.034 ± 0.012 and 0.22 ± 0.05, respectively. They were 0.35 ± 0.09 and 0.93 ± 0.15, 0.349 ± 0.056 and 0.91 ± 0.15, 0.336 ± 0.089 and 0.44 ± 0.05 in endometrial tissues in the embryonic implantation normal pregnancy group;and were 0.62±0.15 and 1.23±0.28, 0.283±0.051 and 0.55±0.09, 0.225±0.065 and 0.35± 0.07 in decidua tissues in the embryonic development normal pregnancy group. The protein expression of chemokines and their receptors in endometrial tissues in the embryonic implantation normal pregnancy group and in decidua tissues in the embryonic development normal pregnancy group were higher than those in the normal unpregnancy group, with statistically significant difference(P<0.05). Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 in decidual tissues in the embryonic development normal pregnancy group were significantly higher(P<0.05), while CCL2 and CCR2, RANTES and CCR5 were significantly lower (P<0.05). (2) Compared with the embryonic implantation normal pregnancy group, CXCL12 and CXCR4 (0.20±0.06 and 0.44±0.11) in endometrial tissues in the embryonic implantation URSA group were significantly lower (P<0.01), while CCL2 and CCR2(0.451±0.133 and 1.32± 0.20), RANTES and CCR5(0.488 ± 0.137 and 0.61 ± 0.18)were higher (P<0.05). (3) Compared with the embryonic development normal pregnancy group, CXCL12 and CXCR4 in decidual tissues of pre-abortion URSA group(0.27 ± 0.09 and 0.26 ± 0.10) , post-abortion URSA group (0.25 ± 0.08 and 0.23 ± 0.08) were significantly lower (P<0.01), while CCL2 and CCR2 (0.576±0.123 and 0.92±0.15 in the pre-abortion URSA group;0.748±0.112 and 1.56±0.34 in the post-abortion URSA group), RANTES and CCR5(0.294±0.054 and 0.59 ± 0.18 in the pre-abortion URSA group;0.363 ± 0.058 and 0.78 ± 0.14 in the post-abortion URSA group) were significantly higher(P<0.05). CCL2 and CCR2, RANTES and CCR5 in decidual tissues in the post-abortion URSA group was obviously higher than those of the pre-abortion URSA group, with statistically significant difference (P<0.05). Couclusions The accurate expression of CXCL12, CCL2, RANTES and their receptors CXCR4, CCR2, CCR5 play important roles in the embryonic implantation and development. The lower expression of CXCL12 and CXCR4 protein and higher expression of CCL2 and CCR2, RANTES and CCR5 in decidua and chorionic tissues are closely related to the pathogenesis of URSA.

Production and mechanism of CCL5 by macrophages in U14 cervical cancer-bearing mice during infection / 中华妇产科杂志

Objective To investigate the production and mechanism of chemokine (C-C motif) ligand 5 (CCL5) by macrophages in U14 cervical cancer-bearing mice during infection. Methods The U14 cervical cancer cells were injected in C57BL/6 mice to induce tumor-bearing condition. Lipopolysaccharide (LPS) was injected into C57BL/6 mice to induce infection. The protein expression of CCL5 in the serum and the CCL5 mRNA expression in inflammatory cells were measured by ELISA and fluorescence quantitative-PCR in four groups. Macrophages were induced in the tumor conditioned medium (TCM) which extracted from mice serum. The protein expression levels of CCL5, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in the medium and CCL5, PGE2 and cAMP mRNA expression in the macrophages were detected in different groups. In order to determine whether the inhibition was related to PGE2, selective cyclooxygenase 2(COX-2) inhibitor NS398 was used to reverse this phenomenon and protein kinase A (PKA) inhibitor H89 demonstrated the mechanism through blocking cAMP/PKA signaling pathway. Results (1) The protein and mRNA level of CCL5 in tumor-bearing mice were respectively (151±35) pg/ml and 1.0, which were lower than those in the tumor-free mice (691 ± 85) pg/ml and 4.5 ± 0.8, there were significant difference between them (all P<0.05). The protein and mRNA level of PGE2 in tumor-bearing mice were (1 198±83) pg/ml and 5.8±0.8, which were higher than those in the tumor-free mice (187±25) pg/ml and 1.0, the difference were significant (all P<0.05). The protein and mRNA level of CCL5 in tumor-free+LPS mice were (4 049±141) pg/ml and 31.5±2.0, which were higher than those in the tumor-bearing+LPS mice (1 951±71) pg/ml and 12.1±2.8, the difference were also significant (P<0.05). The protein and mRNA level of PGE2 in tumor-free+LPS mice were (676±70) pg/ml and 3.4±0.4, which were lower than those in tumor-bearing+LPS mice (2 550±382) pg/ml and 11.6±0.9, the difference were also significant (all P<0.05). (2) Macrophages were cultured in vitro using TCM derived from mice. The protein and mRNA level of CCL5 in tumor-bearing mice TCM were respectively (1 626 ± 177) pg/ml and 28.6 ± 1.2, which were higher than those in the tumor-free mice TCM [(27 ± 3) pg/ml and 1.0], there were significant difference (P<0.05). The protein and mRNA level of PGE2 in tumor-bearing mice TCM were (790 ± 156) pg/ml and 1.7 ± 0.3, which were higher than those in the tumor-free mice TCM [(448 ± 115) pg/ml, 1.0], the difference were significant (all P<0.05). The protein and mRNA level of cAMP in tumor-bearing mice TCM were (164 ± 30) pg/ml and 1.6 ± 0.3, which weres higher than those in the tumor-free mice TCM [(118 ± 25) pg/ml,1.0], the difference were significant (all P<0.05). The protein and mRNA level of CCL5 in tumor-free + LPS mice TCM were (10 475 ± 742) pg/ml and 212.0 ± 5.7, which were higher than those in the tumor-bearing+LPS mice TCM [(6 375±530) pg/ml, 142.3±2.5], the difference were significant (all P<0.05). The protein and mRNA level of PGE2 in tumor-free+LPS mice TCM were (2 438±95) pg/ml and 4.3±0.7, which weres lower than those in the tumor-bearing + LPS mice TCM [(3 441 ± 163) pg/ml, 5.9 ± 0.3], the difference were significant (all P<0.05). The protein and mRNA level of cAMP in tumor-free+LPS mice TCM were (340 ± 13) pg/ml and 4.1 ± 0.4, which were lower than those in the tumor-bearing + LPS mice TCM [(542 ± 42) pg/ml, 5.4 ± 0.5], the difference were significant (all P<0.05). (3) Using COX-2 inhibitor NS398 in the tumor-bearing+LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (7 691±269) pg/ml and 159.0±8.9, (2 820±152) pg/ml and 4.9 ± 0.3, (465 ± 8) pg/ml and 4.3 ± 0.4, respectively, and there were significant difference (all P<0.05), compared to before treatment. Using PKA inhibitor H89 in the tumor-bearing+LPS mice, the protein and mRNA level of CCL5, PGE2 and cAMP were (8 375±520) pg/ml and 177.0±8.8, (2 650±35) pg/ml and 4.7 ± 0.4, (368 ± 13) pg/ml and 3.1 ± 0.7, respectively, and there were significant difference (all P<0.05), compared to before treatment. Conclusion TCM of U14 cells activated macrophages to release PGE2 could inhibit the expression of CCL5 levels by cAMP/PKA signaling pathway.

Ginsenoside metabolites Compound K suppress TNF-α-induced RANTES secretion in human bronchial epithelial cell line / 第二军医大学学报

Objective To explore the effects of ginsenoside metabolite Compound K (CK) on TNF-α-induced RANTES secretion in human bronchial epithelial cell line BEAS-2B and to elucidate its possible mechanism. Methods BEAS-2B cells were cultured and treated with CK in different dosages, and then the secretion of RANTES in BEAS-2B cells exposed to inflammatory stimuli was measured by ELISA kits. Expressions of RANTES mRNA and protein were detected by RT-PCR and Western blotting analysis, respectively. Reporter gene assay was employed to elucidate the interaction between CK and activator protein 1(AP-1), glucocorticoid receptor (GR). CK antagonist mifepristone was used to observe whether the inhibitory effect of CK against RANTES was mediated by GR. Results TNF-α-induced secretion of RANTES in BEAS-2B was markedly inhibited by CK (3-30 μmol/L). Treatment with CK also reduced RANTES mRNA and protein expression. Reporter gene assays indicated that CK was a GR agonist and could repress TNF-α-induced AP-1 transactivation. The inhibitory effects of CK on RANTES secretion were antagonized by mifepristone, suggesting a pivotal role of GR. Conclusion These results suggest that CK may inhibit TNF-α-induced RANTES secretion in human bronchial epithelial cells, which might be associated with GR pathway activation and AP-1 pathway inhibition.

The Evaluation and Significance of RANTES in Serum and Peritoneal Fluid in Patients with Endometriosis / 天津医药

Objective To investigate the role and clinical significance of RANTES in endometriosis (EM). Methods The serum level of RANTES was examined by ELISA in 50 patients with endometriosis (EM group), 32 patients with benign ovarian neoplasms (disease control group) and 30 normal control women (normal control group). The level of RANTES in peritoneal fluid was examined in EM group and disease control group. Results The serum level of RANTES was significantly higher in EM group (108.73±60.69) ng/L than that of disease control group (31.26±20.33) ng/L and normal control group (29.77 ± 11.58) ng/L (P＜0.05). The level of RANTES in peritoneal fluid was significantly higher in EM group (726.31 ± 259.83) ng/L than that of disease control group (116.19 ± 81.64) ng/L (P＜0.05). The levels of RANTES in serum and peritoneal fluid in EM group were positively correlated with clinical stage respectively (rs=0.501 and 0.562,P＜0.01). The level of RANTES in peritoneal fluid in EM group was positively correlated with dysmenorrhea score (rs=0.527,P＜0.01). The serum level of RANTES was positively correlated with the level of RANTES in peritoneal fluid in EM group (rs=0.363, P＜0.05). The levels of RANTES in serum and peritoneal fluid were positively correlated with inflammatory response degree in endometriotic tissues in EM group (rs=0.326 and 0.391,P＜0.05 or P＜0.01).Conclusion Detection of the serum level of RANTES by ELISA may be one of parameters for diagnosis of endometriosis.

Chemokine 5 and its receptor in breast cancer / 国际肿瘤学杂志

Chemokine CCL5 and its receptor CCR5,as one of the chemokine family,are involved in the processes of many diseases and especially play an important role in breast cancer.Recent researches show that chemokine CCL5 and its receptor CCR5 have an obvious impact on the tumorigenesis,invasion,metastasis,therapy and prognosis of breast cancer.

CCL5 triggers new thinking on neuropathic pain / 第二军医大学学报

The mechanism of neuropathic pain is extremely complex. Despite of great research efforts on the pathogenesis of neuropathic pain and development of new drugs in recent years, the mechanism of neuropathic pain remains unclear. CCL5 belongs to the C-C chemokine subfamily, and its abnormal regulation of inflammatory responses under pathological condition may induce or exacerbate a variety of diseases. Recently, many researches have suggested that CCL5 has the potential of mediating neuropathic pain, but with unknown mechanism. This paper reviewed the role of CCL5 in the development and regulation of neuropathic pain and discussed the possibility of CCL5 as an cause of neuropathic pain.

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença / Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.

OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

Effects of lentivirus-mediated CC chemokine ligand 5 (CCL5)-RNAi on biological behaviors of human breast cancer cells (MDA-MB-231) / 中华普通外科杂志

Objective To study the effect of lentivirus-mediated CCL5-RNAi on the biological behaviors of human breast cancer cells. Methods CCL5-specific siRNA gene was synthesized and cloned into the recombinant lentiviral vector, pGCSIL-GFP. Human high-metastatic breast cancer cells, MDA-MB-231, were infected by CCL5-siRNA recombinant lentivirus, which was set as KD group. Cells infected with CCL5-NC was as NC group, and cells cultured was as CON group. The expression of CCL5 mRNA and protein in MDA-MB-231 cells was detected by RT-PCR and western blot, respectively. Cell growth suppression and cell cycle was observed by MTT assay and fluorescence activated cell sorting (FACS). Colony formation and migration ability were determined by colony-rorming assay and Boyden chamber method. Results After infection of CCL5-siRNA recombinant lentivirus, the expression level of CCL5 mRNA and protein in MDA-MB-231 cells as well as the colony formation and migration ability decreased significantly, but cell's proliferation was not affected obviously. Compared with MDA-MB-231 (0.88± 0.15) and MDA-MB-231/CCL5-NC (1.00±0.07) cells, the expression of CCL5 mRNA in MDA-MB-231/ CCL5-siRNA decreased to 0.18±0.03, P<0.01. Compared with MDA-MB-231/CCL5-NC (1.82±0.18) cells, the expression of CCL5 protein in MDA-MB-231/CCL5-siRNA decreased to 0.33±0.13, P <0.01. Colony-forming assay and Boyden chamber method showed that the colony formation and migration ability of MDA-MB-231/CCL5-siRNA decreased markedly (P<0.05). The clone count in KD group was (0.33± 0.10), which was a significant decrease from (0.97±0.09) (NC group) and (1.04±0.07) (CON group), P<0.05. The number of cells that migrated through the chamber membrane of KD group (38± 15) was less than that of NC group (77±11, P <0.05) and CON group (69±9, P <0.05). However, MTT assay and FACS revealed that the proliferation of MDA-MB-231/CCL5-siRNA was not different from MDA-MB-231/CCL5-NC and MDA-MB-231 (P>0.05), the proliferation index (PI) of group KD, NC and CON were (0.48±0.02), (0.44±0.05) and (0.47±0.02) respectively. The difference was not statistically significant by multiple comparison (P>0.05). Conclusion CCL5-specific siRNA can specifically suppress the colony formation and migration of human high-matastatic breast cancer cells.

Downregulation of Angiotensin II-Induced 12-Lipoxygenase Expression and Cell Proliferation in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats by CCL5

Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 (AT2) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the AT2 receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an AT2 receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the AT2 receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.

LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression

Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.