The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC). Stromal syntenin deficiency, in turn, generates a pro-tumoral microenvironment. From serial transplantations in mice and co-culture experiments, we conclude that syntenin-deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro-tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML–stroma crosstalk and unsuspected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.

中文翻译：

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基质联蛋白的下调维持 AML 的发展

癌症和基质细胞之间的串扰在肿瘤进展中起着至关重要的作用。Syntenin 是一种参与细胞间通讯调节的小支架蛋白，正在成为癌症治疗的靶点。在这里，我们发现某些侵袭性形式的急性髓系白血病（AML）会降低骨髓基质细胞（BMSC）中联腱蛋白的表达。基质连蛋白缺乏反过来会产生促肿瘤微环境。通过对小鼠的连续移植和共培养实验，我们得出结论，缺乏联腱蛋白的 BMSC 通过促进 AML 细胞存活和蛋白质合成来刺激 AML 侵袭性。这种促肿瘤活性得到内皮糖蛋白表达增加的支持，内皮糖蛋白是 BMSC 的经典标记物，反式刺激 AML 翻译活性。简而言之，我们的研究揭示了 AML 间质串扰的潜在核心恶性信号循环以及 Syntenin 意想不到的肿瘤抑制作用，在癌症治疗中对 Syntenin 进行全身靶向治疗时需要考虑这些作用。