ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes.
ICAM1 expression is induced by proinflammatory cytokines and associated with TLS formation in aggressive breast cancer subtypes.
复制标题
DOI：
10.1038/s41598-018-29604-2
复制
发表时间：
2018-08-06
影响因子：
4.6
通讯作者：
Fenton KA
中科院分区：
文献类型：
--
作者：
Figenschau SL;Knutsen E;Urbarova I;Fenton C;Elston B;Perander M;Mortensen ES;Fenton KA
认为肿瘤微环境内三级淋巴样结构（TLS）的瘤内形成是抗肿瘤应答期间抗原激发的结果。细胞内粘附分子1（ICAM 1）除了与三阴性乳腺癌（TNBC）有关外，还与多种免疫和炎症反应有关。在这项研究中，我们在侵袭性肿瘤表型TNBC、HER 2+和管腔B中检测到TLS，而TLS阴性组仅包含管腔A亚型的肿瘤。我们发现ICAM 1仅在TNBC和HER 2富集亚型中表达，已知这些亚型与炎症和TLS形成相关。此外，正常乳腺上皮细胞和乳腺癌细胞系在促炎细胞因子TNFα、IL 1 β和IFNγ刺激下表达ICAM 1。在MCF 7、MDA-MB-468和SK-BR-3细胞中诱导ICAM 1过表达，而与激素受体状态无关。总之，我们的研究结果表明，ICAM 1在乳腺癌的侵袭性亚型中表达，并且其表达可由众所周知的促炎细胞因子诱导。ICAM 1可能是TNBC的一个有吸引力的分子靶点，但阐明ICAM 1在靶向治疗中的作用的进一步研究必须考虑乳腺癌的选择性亚型。
Intratumoral formation of tertiary lymphoid structures (TLS) within the tumor microenvironment is considered to be a consequence of antigen challenge during anti-tumor responses. Intracellular adhesion molecule 1 (ICAM1) has been implicated in a variety of immune and inflammatory responses, in addition to associate with triple negative breast cancer (TNBC). In this study, we detected TLS in the aggressive tumor phenotypes TNBC, HER2+ and luminal B, whereas the TLS negative group contained solely tumors of the luminal A subtype. We show that ICAM1 is exclusively expressed in TNBC and HER2 enriched subtypes known to be associated with inflammation and the formation of TLS. Furthermore, cell from normal mammary epithelium and breast cancer cell lines expressed ICAM1 upon stimulation with the proinflammatory cytokines TNFα, IL1β and IFNγ. ICAM1 overexpression was induced in MCF7, MDA-MB-468 and SK-BR-3 cells regardless of hormone receptor status. Taken together, our findings show that ICAM1 is expressed in aggressive subtypes of breast cancer and its expression is inducible by well-known proinflammatory cytokines. ICAM1 may be an attractive molecular target for TNBC, but further investigations elucidating the role of ICAM1 in targeted therapies have to take into consideration selective subtypes of breast cancer.
登录
查看更多内容
影响因子：
8.8
作者：
Mohammed, Z. M. A.;Going, J. J.;Edwards, J.;Elsberger, B.;McMillan, D. C.
通讯作者：
McMillan, D. C.
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.4
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
11.5
作者：
Lin, Yi-Chu;Shun, Chia-Tung;Chen, Ching-Chow
通讯作者：
Chen, Ching-Chow
影响因子：
12.3
作者：
Langmead B;Trapnell C;Pop M;Salzberg SL
通讯作者：
Salzberg SL