CD44 is a type I transmembrane glycoprotein interacting with a number of extracellular components, including hyaluronic acid (HA). CD44-HA axis is involved in a variety of processes, including adhesion, migration, differentiation, trafficking, and others. CD44 is overexpressed in several cancers where binding of HA induces signal transduction leading to activation of antiapoptotic proteins and factors linked to drug resistance. As such, CD44 has been implicated in cancer growth, progression, and metastasis. It has been convincingly demonstrated that blocking CD44-HA interaction decreases cancer cell survival and metastasis. In this study, using in vitro selection, we have developed DNA aptamers recognizing a HA-binding domain of CD44 with high affinity and specificity. The aptamers bind to CD44 with nanomolar affinities and efficiently inhibit the growth of leukemic cancer cells characterized by high expression of CD44. The selectivity is demonstrated by an irrelevant effect on cells characterized by low CD44 levels. The obtained aptamers broaden the existing landscape of potential approaches to the development of antitumor strategies based on inhibition of the CD44 axis.

中文翻译：

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抗 CD44 DNA 适体选择性靶向癌细胞。

CD44 是一种 I 型跨膜糖蛋白，与许多细胞外成分相互作用，包括透明质酸 (HA)。CD44-HA 轴参与多种过程，包括粘附、迁移、分化、运输等。CD44 在几种癌症中过度表达，其中 HA 的结合诱导信号转导，导致抗凋亡蛋白和与耐药性相关的因子的激活。因此，CD44 与癌症的生长、进展和转移有关。已经令人信服地证明，阻断 CD44-HA 相互作用会降低癌细胞的存活和转移。本研究采用体外选择，我们开发了 DNA 适体识别 CD44 的 HA 结合域，具有高亲和力和特异性。适配体以纳摩尔亲和力与 CD44 结合，并有效抑制以 CD44 高表达为特征的白血病癌细胞的生长。对以低 CD44 水平为特征的细胞的无关影响证明了选择性。获得的适体拓宽了现有的基于 CD44 轴抑制的抗肿瘤策略开发的潜在方法。