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转移是肿瘤患者死亡最常见的原因,而淋巴转移是大多数肿瘤转移的主要途径之一。近年来,CC趋化因子配体21 (CC chemokine ligand 21,CCL21) 及其受体CC趋化因子受体7型 (CC chemokine receptor type 7,CCR7) 在淋巴转移中的作用逐渐受到关注。CCL21主要由淋巴内皮细胞产生,其与树突状细胞 (Dendritic cells,DCs) 和T细胞等表面CCR7的相互作用是免疫细胞淋巴迁移及淋巴结归巢的主要决定因素。然而,表达CCR7的肿瘤细胞也可以利用类似的机制进入淋巴管进行淋巴转移。如何靶向CCL21/CCR7轴,既能抑制淋巴转移,又不影响抗肿瘤免疫反应已成为肿瘤免疫治疗研究的重要议题。文中将对CCL21/CCR7轴在淋巴转移中的作用及其作为靶点治疗肿瘤转移的临床前和临床试验研究进行综述,为靶向CCL21/CCR7信号轴治疗肿瘤转移的相关研究提供参考。 相似文献
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乳腺癌是发生在乳腺腺上皮组织的恶性肿瘤,是全世界女性死亡的最常见原因之一。趋化因子CCL21是一种具有趋化细胞迁移功能的低分子量蛋白质,CCL21可以与淋巴细胞表面表达的CCR7受体结合,促使其迁移至乳腺肿瘤相关部位;同时还能与乳腺肿瘤细胞上表达的CCR7配体结合,使其不断向正常部位转移和侵袭,从而导致癌细胞恶性发展。CCL21/CCR7轴与乳腺癌的治疗、转移、侵袭与预后有着密切联系。我们简要综述近年来CCL21/CCR7轴与乳腺癌的转移及治疗相关研究进展,以期为乳腺癌的临床治疗提供参考。 相似文献
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整合素是肿瘤微环境的重要组成部分,是广泛存在于细胞膜表面的黏附分子,可以识别并结合细胞外基质中相应的配体,参与许多重要的生理过程,包括肿瘤转移.整合素可以促进肿瘤转移的各个阶段,肿瘤微环境也会反过来影响整合素的表达,从而促进癌症的发生发展. 相似文献
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《生物化学与生物物理进展》2017,(8)
整合素是肿瘤微环境的重要组成部分,是广泛存在于细胞膜表面的黏附分子,可以识别并结合细胞外基质中相应的配体,参与许多重要的生理过程,包括肿瘤转移.整合素可以促进肿瘤转移的各个阶段,肿瘤微环境也会反过来影响整合素的表达,从而促进癌症的发生发展. 相似文献
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盘状结构域受体2(discoidin domain receptor2,DDR2)一种受体型酷氨酸蛋白激酶,其配体为纤维型胶原。胶原诱导的DDR2磷酸化可上调细胞基质金属蛋白酶1的过表达。DDR2在人体内广泛分布并与肿瘤的转移相关。为进一步研究DDR2在肿瘤转移中的作用和DDR2在细胞内的信号通路,对DDR2的胞外区进行了原核融合表达并纯化可溶性部分,获得纯度约85%的纯化蛋白,竞争结合抑制实验证明,纯化的融合蛋白可以特异性阻断Ⅱ型胶原与天然DDR2受体的结合。 相似文献
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受体酪氨酸激酶 c-Met 是抗肿瘤治疗的一个重要靶点,c-Met/HGF 通路在肿瘤的发生、发展、转移及血管再生中发挥重要作用。
综述 c-Met 及与配体 HGF 的复合物结构特征、c-Met/HGF 通路的生物学作用以及靶向 c-Met 抗肿瘤小分子抑制剂的研究进展。 相似文献
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JAK信号通路通过配体和细胞表面的受体相互结合而诱导受体二聚化及磷酸化,激活JAK.活化的JAK-STAT信号通路参与肿瘤的发生、发展、血管新生、侵袭和转移.在BCR-ABL阴性骨髓增殖性肿瘤(MPN)中JAK2、MPL及CALR基因突变均可组成性激活JAK2-STAT5信号通路.因此JAK-STAT通路成为研究的热点... 相似文献
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《生理学报》2021,(2)
整合素是一类由α和β两个亚基组成的异源二聚体单次跨膜细胞黏附分子,通过与其对应配体相互作用,介导细胞与细胞、细胞与胞外基质之间的黏附,同时可以将细胞外信号传递至胞内,并招募一系列胞内蛋白与整合素胞内段结合,在细胞膜上形成超分子结构,激活下游信号。整合素的活化进程伴随着其胞外结构域由折叠构象转变为伸展构象以及胞内结构域的彼此分离。在细胞迁移过程中,整合素参与黏着斑的形成,连接胞外基质和细胞骨架,传递胞内-胞外的力学信号驱使细胞迁移。肿瘤微环境介导的整合素活化可促进多种类型细胞向肿瘤部位迁移,共同实现血管生成及肿瘤转移。本文对整合素的活化过程,其介导黏着斑动态变化引发的细胞迁移及对肿瘤转移的影响进行综述。 相似文献
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Risto Renkonen Pirkko Mattila Marja-Leena Majuri Jarkko Rabina Sanna Toppila Jutta Renkonen Laura Hirvas Jaana Niittymaki Juha Pekka Turunen Ossi Renkonen Timo Paavonen 《Glycoconjugate journal》1997,14(5):593-600
Extravasation from the blood of malignant tumour cells that form metastasis and leukocytes that go into tissues require contact
between selectins and their sialyl Lewis x and sialyl Lewis a (sLex and sLea respectively) decorated ligands. Endothelial
cells have been shown to express sLex epitopes in lymph nodes and at sites of inflammation, and this is crucial for the selectin-dependent
leukocyte traffic. Besides the ability to synthesize sLex on sialylated N-acetyllactosamine via the action of α(1,3)fucosyltransferase(s),
endothelial cells can also degrade sLex to Lewis x through the action of α(2,3)sialidase(s). In addition, several epithelial
tumors possess the machinery to synthesize sLex, which facilitates their adhesion to endothelial E- and P-selectin.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
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目的:观察肺癌患者外周血血小板对肺癌分期和血行转移的影响。方法:选择在我院呼吸科初诊的原发性肺癌患168例,分析其外周血小板计数与肺癌病理类型和分期的关系,并在模拟流体状态下,体外研究活化血小板对培养的肺癌细胞和内皮细胞相互作用的影响。结果:肺腺癌中外周血血小板计数增高现象最为明显,占37.09%(23/62)(P〈0.05),鳞癌占22.64%,小细胞癌占22.70%,其他占14.20%。其中有远处血行转移者血小板增多(20.24%)较无明显转移者(7.14%)相差显著(P〈0.01)。同时体外研究显示流体状态对肺癌细胞粘附存在影响,而活化血小板增强了肺癌细胞与内皮细胞的相互作用。结论:血小板活化与肺癌尤其是肺腺癌的血行转移密切相关;活化血小板增强了肺癌细胞与内皮细胞的相互作用是血小板促进肺癌血行转移的重要机制之一。 相似文献
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Arndt NX Tiralongo J Madge PD von Itzstein M Day CJ 《Journal of cellular biochemistry》2011,112(9):2230-2240
Currently there is only a modest level knowledge of the glycosylation status of immortalised cell lines that are commonly used in cancer biology as well as their binding affinities to different glycan structures. Through use of glycan and lectin microarray technology, this study has endeavoured to define the different bindings of cell surface carbohydrate structures to glycan-binding lectins. The screening of breast cancer MDA-MB435 cells, cervical cancer HeLa cells and colon cancer Caco-2, HCT116 and HCT116-FM6 cells was conducted to determine their differential bindings to a variety of glycan and lectin structures printed on the array slides. An inverse relationship between the number of glycan structures recognised and the variety of cell surface glycosylation was observed. Of the cell lines tested, it was found that four bound to sialylated structures in initial screening. Secondary screening in the presence of a neuraminidase inhibitor (4-deoxy-4-guanidino-Neu5Ac2en) significantly reduced sialic acid binding. The array technology has proven to be useful in determining the glycosylation signatures of various cell-lines as well as their glycan binding preferences. The findings of this study provide the groundwork for further investigation into the numerous glycan-lectin interactions that are exhibited by immortalised cell lines. 相似文献
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肝素作为传统抗凝剂,常用来治疗癌症患者静脉血栓。临床和实验数据证实,肝素具有抗肿瘤活性。同时也有大量研究发现,肝素有抗肿瘤转移的作用。肝素可以通过各种机制抑制肿瘤转移,包括抑制细胞间的相互作用;抑制肝素酶的表达;调节各种生长因子以及调节机体凝血功能等。选凝素(seletin)是介导肿瘤转移初始阶段的重要因子,而肝素能够抑制选凝素介导的的肿瘤细胞与白细胞、血小板及内皮细胞的相互作用,从而达到抗转移的效果。本文综述了肝素抑制选凝素介导的肿瘤转移的作用机制,为肝素在抗肿瘤转移方面的临床应用提供参考。 相似文献
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Reiji Kannagi 《Glycoconjugate journal》1997,14(5):577-584
The carbohydrate determinants, sialyl Lewis A and sialyl Lewis X, which are frequently expressed on human cancer cells, serve
as ligands for a cell adhesion molecule of the selectin family, E-selectin, which is expressed on vascular endothelial cells.
These carbohydrate determinants are involved in the adhesion of cancer cells to vascular endothelium and thus contribute to
hematogenous metastasis of cancer. The initial adhesion mediated by these molecules triggers activation of integrin molecules
through the action of several cytokines and leads to the extravasation of cancer cells. Cancer cells also produce humoral
factors that facilitate E-selectin expression on endothelial cells. The degree of expression of the carbohydrate ligands at
the surface of cancer cells is well correlated with the frequency of hematogenous metastasis and prognostic outcome of patients
with cancers. The alteration of glycosyltransferase activities that leads to the enhanced expression of these carbohydrate
ligands on cancer cell surface are currently being investigated.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
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Weilan Ye 《The EMBO journal》2014,33(8):786-787
Since metastatic lesions of solid tumors are the major cause of mortality in cancer patients, understanding the molecular mechanisms of metastasis is of paramount importance. Although extensive knowledge has been accumulated regarding the early steps in metastasis—starting with the departure of cancer cells from their primary sites, to their transit through the hematogenous and/or lymphatic systems, and ending with their entrance into the parenchyma of distant organs—it is difficult if not impossible to translate such knowledge into medicine due to the challenge of identifying patients with only primary tumors but otherwise pristine organs. In other words, autopsy studies indicate that a large proportion of patients already harbor dormant, undetectable micrometastases at the time of cancer diagnosis (Hensel et al, 2013 ). Accordingly, stopping tumor cell dissemination is too late for these patients. Therefore, understanding the survival and outgrowth of micrometastases may hold greater promise to combat metastatic disease. 相似文献
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Most of the cancer cells arrested in the microcirculation during hematogenous metastasis are rapidly killed; one major mechanism is surface-membrane rupture, associated with the mechanical deformation of cancer cells in capillaries. The feasibility of increasing the susceptibility of cancer cells to lethal, deformation-associated trauma by doxorubicin, was tested in an in vitro mechanical model system, by filtering suspensions of L1210 leukemia cells through 8-μm pore-size Nuclepore® membranes, with or without prior incubation with 10-7M doxorubicin. The results showed that mechanically-induced loss of cancer cells immediately after filtration was increased from 18 to 55% in cells previously exposed to doxorubicin for 48 h. The results indicate the feasibility of chemotherapeutic enhancement of the mechanical killing-action of the microvasculature as a potential rate-regulator of hematogenous metastasis. 相似文献
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Magnani JL 《Archives of biochemistry and biophysics》2004,426(2):122-131
The discoveries of sialylated, fucosylated lacto-, and neolacto-type carbohydrate structures were accomplished with the aid of analytical methods and monoclonal antibodies such as the immunostaining of thin layer chromatograms. Based on the use of such antibodies, these structures, notably sialyl Le(a) and sialyl Le(x), were demonstrated to be highly expressed in many malignant cancers. A diagnostic assay using one of these antibodies (CA19-9) is now established as one of the more commonly used assays for pancreatic and gastrointestinal cancers worldwide. Upon further study, several laboratories have demonstrated that the level of expression of these carbohydrate tumor markers is also positively correlated with patient survival and is a prognostic indicator of metastatic disease. Concurrent with this finding, both sialyl Le(a) and sialyl Le(x) were shown to bind to a family of carbohydrate-binding proteins involved in the extravasation of cells from the bloodstream, called the selectins. Thus, sialyl Le(a) and sialyl Le(x) expressed on cell surfaces play functional roles in medical conditions that require extravasation of cells from the bloodstream which include a wide range of inflammatory diseases and cancer metastasis. Many studies have confirmed the function of sialyl Le(a) and sialyl Le(x) in animal models of these diseases and the inhibition of binding of sialyl Le(a) and sialyl Le(x) to the selectins is a validated drug target in the pharmaceutical industry. Thus, a new class of drugs, arising from the field of glycobiology, is based on the rational design of small molecule drugs that mimic the structures sialyl Le(a) and sialyl Le(x) and can potently inhibit their functional binding to the selectins. 相似文献
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Dongmei Diao Zhe Wang Yao Cheng Hao Zhang Qi Guo Yongchun Song Kun Zhu Kang Li Di Liu Chengxue Dang 《PloS one》2014,9(7)
Background
Plasma D-dimer levels have been shown to be high in advanced tumor stage patients and can be used to predict clinical outcome in cancer patients. As most advanced tumor stage patients exhibit asymptomatic metastasis, which contributes to early tumor recurrence after surgery, we hypothesized that plasma D-dimer levels can be used to predict patients with potential metastasis.Methods
We enrolled 1042 primary gastric cancer patients in three multiple cancer centers in Northwest China and examined plasma D-dimer levels using the latex-enhanced immunoturbidimetric assay (LEIA) method. Plasma D-dimer levels were compared with the clinicopathological characteristics in this large-scale case-control study with follow up. We also performed regular follow-up studies for 395 patients to analyze the 2-year survival rate and early tumor recurrence.Results
In this large-scale clinical study, we found that plasma D-dimer levels were increased in patients with distant metastasis and especially hematogenous metastasis patients. The cut-off value of the D-dimer levels was determined to be 1.5 mg/ml based on the ROC curve, and the sensitivity and specificity for metastasis prediction were 61.9% and 86.6%, respectively. Additionally, patients with high D-dimer levels displayed early tumor recurrence and poor outcome during the follow-up study.Conclusion
Plasma D-dimer may represent an easy to measure and lower cost marker for the testing of gastric cancer patients to predict asymptomatic hematogenous metastasis. 相似文献20.
Complement is one of primary defense mechanisms against intravascular microorganisms and could play a role in the immune response
to malignancy and hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA associates with outcome
in patients with breast carcinoma. Genotyping for C1qA[276A/G] was performed in 63 breast cancer subjects with localized tumor and compared with that in 38 breast cancer subjects with
metastasis. Established risk factors for clinical outcome were considered and evaluated in multivariable analysis. Breast
cancer subjects with heterozygous or homozygous C1qA[276G] genotype had a higher rate of metastasis than subjects with the homozygous C1qA[276A] genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1–4.1]. This association was stronger when only metastatic
sites associated with hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR 3.5, 95% CI 1.4–5.6) and
remained statistically significant after adjustment for the number of positive lymph nodes, estrogen receptor status, and
progesterone receptor status. There was no statistical difference in the C1qA[276A/G] allelic distribution between all subjects with breast cancer and controls. These results suggest there could be an association
of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites
linked to hematogenous spread of disease. The C1qA polymorphism associated with decreased distant metastasis has also been
correlated with an increased incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an altered immune
response may play a role in the observed association.
Supported in part by National Institute of Health grant R21-CA90822, Friends You Can Count On! grant 1-87093-00, and the Woody and Louise White Cancer Research Fund. 相似文献