The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

Expressions of CCR7 and CXCR4 Are Associated with Differentiation in Gastrointestinal Cancer

Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association between their expressions and the clinicopathological features in gastrointestinal cancer. Method: 27 paired tissue samples from patients who had curative surgery for gastrointestinal cancer were obtained. Quantitative real-time PCR, immunochemistry assay and western blot analysis were carried out to investigate the expressions of CCR7, CXCR4 expressions in gastrointestinal cancer. Results: The cancer tissues expressed significant higher level of CCR7 (P = 0.000) and CXCR4 (P = 0.000) protein than the adjacent normal mucosa. Expressions of CCR7 (P = 0.002) and CXCR4 (P = 0.003) protein in cancer tissues exhibited significant correlation with differentiation in gastrointestinal cancer. Conclusion: Expressions of CCR7 and CXCR4 protein were associated with differentiation in gastrointestinal cancer. CCR7 and CXCR4 may be predictive factors for poor prognosis in patients with gastrointestinal cancer.

不同来源的CC类趋化因子5对人乳腺癌MCF-7细胞侵袭能力影响及其作用机制研究

目的 观察不同来源的CC类趋化因子5（CC chemokine ligand 5,CCL5）对人乳腺癌细胞侵袭能力影响并探讨其作用机制.方法 CCL5特异性siRNA慢病毒载体转染人乳腺癌MCF-7细胞,分别用RT-PCR和Western Blot检测细胞CCL5 mRNA和蛋白表达水平,并用细胞侵袭实验检测转染前后细胞侵袭能力的变化.同时,以不同浓度的外源性rhCCL5 （recombinant human CCL5） 作为趋化因素,用细胞侵袭实验检测MCF-7细胞侵袭能力及CC类趋化因子受体5（CCR5）单克隆抗体细胞侵袭能力的影响.结果 CCL5-siRNA慢病毒载体感染可有效降低CCL5 在MCF-7细胞内的表达,细胞的侵袭指数无明显改变,干扰组和阴性对照组侵袭指数差异无统计学意义（P〉0.05）.rhCCL5可以明显诱导MCF-7细胞的侵袭（P〈0.05）,并且呈浓度依赖趋势;但是这种诱导作用可以部分地被CCR5单克隆抗体阻断,阻断前后细胞的侵袭指数分别为（7.51±0.77）和（3.34±0.51）,差异有统计学意义（P〈0.05）.结论 细胞内表达的CCL5水平变化对乳腺癌细胞MCF-7的侵袭能力没有影响,而外源性CCL5 可以明显增强MCF-7细胞的侵袭,其机制之一可能是通过与细胞表面的CCR5受体结合.

CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (chi(2) = 6.669, P = 0.010; chi(2) = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.

CCR7和VEGF-D蛋白在乳腺癌发生发展过程中的表达及意义

目的研究趋化因子受体7（CCR7）蛋白和血管内皮生长因子D（VEGF-D）蛋白在乳腺癌癌变过程中,即正常乳腺组织、轻中度导管非典型增生组织、重度导管非典型增生＋导管原位癌组织及乳腺浸润性导管癌组织中的表达及意义。方法采用免疫组化染色法,检测正常乳腺组织（n=20）、乳腺轻中度导管非典型增生组织（n=20）、乳腺重度导管非典型增生＋导管原位癌组织（n=20）及乳腺浸润性导管癌组织（n=73）中CCR7和VEGF-D蛋白的表达情况,并根据D2-40染色结果计算微淋巴管密度（LMVD）。同时分析乳腺癌组织中,CCR7和VEGF-D蛋白表达与乳腺癌临床病理学特征的关系、CCR7和VEGF-D蛋白表达与LMVD值间的关系及CCR7蛋白表达与VEGF-D蛋白表达的关系。结果 1正常乳腺组织组〔CCR7蛋白：0（0/20）,VEGF-D蛋白：5.0%（1/20）〕）、轻中度乳腺导管非典型增生组〔CCR7蛋白：5.0%（1/20）,VEGF-D蛋白：20.0%（4/20）〕）、乳腺重度导管非典型增生＋导管原位癌组〔CCR7蛋白：30.0%（6/20）,VEGF-D蛋白：40.0%（8/20）〕）及乳腺癌组〔CCR7蛋白：47.9%（35/73）,VEGF-D蛋白：57.5%（42/73）〕的CCR7蛋白（χ^2趋势=23.905,P〈0.050）和VEGF-D蛋白（χ^2趋势=22.349,P〈0.050）的表达阳性率逐渐增高。2正常乳腺组织组、乳腺轻中度导管非典型增生组、乳腺重度导管非典型增生＋导管原位癌组及乳腺癌组的LMVD值分别为2.00±1.02、6.70±3.48、9.01±2.13及16.32±4.07,LMVD值逐渐增高,4组间两两比较差异均有统计学意义（P〈0.050）。3在乳腺癌患者中,CCR7蛋白和VEGF-D蛋白的表达均与临床分期、组织学分级、淋巴结转移及人类表皮生长因子2（HER-2）表达有关（P〈0.050）,组织学分级越高、临床分期为Ⅲ＋Ⅳ期（与Ⅰ＋Ⅱ期者相比）、淋巴结转移（与未发生淋巴结转移者相比）及HER-2表达阳性（与HER-2表达阴性者相比）者CCR7蛋白和VEGF-D蛋白的表达阳性率较高。在乳腺癌患者中,LMVD值和VEGF-D蛋白表达强度之间呈正相关性（r=0.623,P〈0.010）,而LMVD值与CCR7蛋白表达程度之间的相关性无统计学意义（r=-0.303,P〉0.050）。在乳腺癌组织中,CCR7蛋白表达与VEGF-D蛋白表达间呈弱正相关性（r=0.112,P〈0.050）。结论 CCR7蛋白和VEGF-D蛋白的表达水平在一定程度上提示了乳腺导管非典型增生向乳腺癌的转化潜能,其表达可作为判断乳腺癌恶性生物学行为的重要指标。

Dendritic cell migration in inflammation and immunity

Dendritic cells(DCs)are the key link between innate immunity and adaptive immunity and play crucial roles in both the promotion of immune defense and the maintenance of immune tolerance.The trafficking of distinct DC subsets across lymphoid and nonlymphoid tissues is essential for DC-dependent activation and regulation of inflammation and immunity.DC chemotaxis and migration are triggered by interactions between chemokines and their receptors and regulated by multiple intracellular mechanisms,such as protein modification,epigenetic reprogramming,metabolic remodeling,and cytoskeletal rearrangement,in a tissue-specific manner.Dysregulation of DC migration may lead to abnormal positioning or activation of DCs,resulting in an imbalance of immune responses and even immune pathologies,including autoimmune responses,infectious diseases,allergic diseases and tumors.New strategies targeting the migration of distinct DC subsets are being explored for the treatment of inflammatory and infectious diseases and the development of novel DC-based vaccines.In this review,we will discuss the migratory routes and immunological consequences of distinct DC subsets,the molecular basis and regulatory mechanisms of migratory signaling in DCs,and the association of DC migration with the pathogenesis of autoimmune and infectious diseases.