Human Endogenous Retrovirus K in the Crosstalk Between Cancer Cells Microenvironment and Plasticity: A New Perspective for Combination Therapy.
Human Endogenous Retrovirus K in the Crosstalk Between Cancer Cells Microenvironment and Plasticity: A New Perspective for Combination Therapy.
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DOI：
10.3389/fmicb.2018.01448
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发表时间：
2018
影响因子：
5.2
通讯作者：
Matteucci C
中科院分区：
文献类型：
--
作者：
Balestrieri E;Argaw-Denboba A;Gambacurta A;Cipriani C;Bei R;Serafino A;Sinibaldi-Vallebona P;Matteucci C
人类内源性逆转录病毒(HERV)的异常激活与多种疾病有关，如癌症、自身免疫和神经疾病。特别是，在癌症中，HERV的活性和表达与肿瘤侵袭性和患者预后特别相关。癌细胞的侵袭性与获得基于细胞干性特征的特殊可塑性和异质性密切相关，也与癌细胞与微环境之间的串扰密切相关。后者是获得侵袭性表型的驱动因素，与转移和对传统癌症治疗的耐药性有关。值得注意的是，在不同的细胞类型和发育阶段，Herv的表达主要受表观遗传机制的调控，并根据周围的微环境受到非常精确的时间和空间调节。聚焦于我们关于Herv-K参与黑色素瘤细胞侵袭性和可塑性的研究经验，这一视角旨在强调Herv-K在癌细胞和肿瘤微环境之间的串扰中的作用。对针对HERV和标准方法的联合治疗的含义进行了讨论。
Abnormal activation of human endogenous retroviruses (HERVs) has been associated with several diseases such as cancer, autoimmunity, and neurological disorders. In particular, in cancer HERV activity and expression have been specifically associated with tumor aggressiveness and patient outcomes. Cancer cell aggressiveness is intimately linked to the acquisition of peculiar plasticity and heterogeneity based on cell stemness features, as well as on the crosstalk between cancer cells and the microenvironment. The latter is a driving factor in the acquisition of aggressive phenotypes, associated with metastasis and resistance to conventional cancer therapies. Remarkably, in different cell types and stages of development, HERV expression is mainly regulated by epigenetic mechanisms and is subjected to a very precise temporal and spatial regulation according to the surrounding microenvironment. Focusing on our research experience with HERV-K involvement in the aggressiveness and plasticity of melanoma cells, this perspective aims to highlight the role of HERV-K in the crosstalk between cancer cells and the tumor microenvironment. The implications for a combination therapy targeted at HERVs with standard approaches are discussed.