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不同类型乳腺癌细胞之间侵袭性特征的侧向传播证据。

Evidence of lateral transmission of aggressive features between different types of breast cancer cells.

机构信息

PhD Program in Biomedical Science, Medicine Faculty, National Autonomous University of Mexico, University City, Mexico City 04510, Mexico.

Department of Molecular Biomedicine, Centre for Investigation and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico City 07360, Mexico.

出版信息

Int J Oncol. 2017 Nov;51(5):1482-1496. doi: 10.3892/ijo.2017.4128. Epub 2017 Sep 19.

Abstract

Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral heterogeneity and tumor cell plasticity importantly contribute to disease progression and treatment failure. However, the dynamic interactions between different tumor clones, as well as their contribution to tumor aggressiveness are still poorly understood. In this study, we provide evidence of a lateral transmission of aggressive features between aggressive and non-aggressive tumor cells, consisting of gain of expression of cancer stem cell markers, increased expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in response to CXCL12, which correlated with high levels of secretion of pro-inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2 by the aggressive cells. Noteworthy, we found no evidence of a TGF-β participation in the inducible-invasive phenotype. Altogether, our results provide evidence of communication between tumor cells with different potentials for aggressiveness, which could influence intra-tumoral population dynamics promoting the emergence of clones with novel functions. Understanding these interactions will provide better targets for diagnosis, prognosis and therapeutic strategies.

摘要

乳腺癌(BrC)是全球主要的公共卫生问题。肿瘤内异质性和肿瘤细胞可塑性对疾病进展和治疗失败有重要贡献。然而,不同肿瘤克隆之间的动态相互作用及其对肿瘤侵袭性的贡献仍知之甚少。在这项研究中,我们提供了证据表明侵袭性和非侵袭性肿瘤细胞之间存在侵袭特征的横向传递,包括癌症干细胞标志物表达增加、CXCL12 受体 CXCR4 和 CXCR7 表达增加以及对 CXCL12 的侵袭性增加,这与侵袭性细胞高水平分泌促炎介质 G-CSF、GM-CSF、MCP-1、IL-8 和金属蛋白酶 1 和 2 相关。值得注意的是,我们没有发现 TGF-β参与诱导性侵袭表型的证据。总之,我们的研究结果提供了证据表明具有不同侵袭潜能的肿瘤细胞之间存在通讯,这可能影响肿瘤内群体动态,促进具有新功能的克隆的出现。了解这些相互作用将为诊断、预后和治疗策略提供更好的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8e/5643070/cfcec4f591b5/IJO-51-05-1482-g00.jpg

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