Gentile Pietro, Garcovich Simone
Surgical Science Department, Plastic and Reconstructive Surgery Unit, University of "Tor Vergata", 00133 Rome, Italy.
Institute of Dermatology, F. Policlinico Gemelli IRCSS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
J Clin Med. 2019 Jun 15;8(6):855. doi: 10.3390/jcm8060855.
Adipose-derived stem cells (ASCs) have been routinely used from several years in regenerative surgery without any definitive statement about their potential pro-oncogenic or anti-oncogenic role. ASCs has proven to favor tumor progression in several experimental cancer models, playing a central role in regulating tumor invasiveness and metastatic potential through several mechanisms, such as the paracrine release of exosomes containing pro-oncogenic molecules and the induction of epithelial-mesenchymal transition. However, the high secretory activity and the preferential tumor-targeting make also ASCs a potentially suitable vehicle for delivery of new anti-cancer molecules in tumor microenvironment. Nanotechnologies, viral vectors, drug-loaded exosomes, and micro-RNAs (MiR) represent additional new tools that can be applied for cell-mediated drug delivery in a tumor microenvironment. Recent studies revealed that the MiR play important roles in paracrine actions on adipose-resident macrophages, and their dysregulation has been implicated in the pathogenesis of obesity, diabetes, and diabetic complications as wounds. Numerous MiR are present in adipose tissues, actively participating in the regulation of adipogenesis, adipokine secretion, inflammation, and inter-cellular communications in the local tissues. These results provide important insights into Adipocyte-secreted exosomal microRNA (A-SE-MiR) function and they suggest evaluating the potential role of A-SE-MiR in tumor progression, the mechanisms underlying ASCs-cancer cell interplay and clinical safety of ASCs-based therapies.
脂肪来源干细胞(ASCs)多年来一直在再生手术中常规使用,但对于它们潜在的促癌或抗癌作用尚无明确说法。在多个实验性癌症模型中,ASCs已被证明有利于肿瘤进展,通过多种机制在调节肿瘤侵袭性和转移潜能方面发挥核心作用,比如含有促癌分子的外泌体的旁分泌释放以及上皮-间质转化的诱导。然而,高分泌活性和对肿瘤的优先靶向性也使ASCs成为在肿瘤微环境中递送新型抗癌分子的潜在合适载体。纳米技术、病毒载体、载药外泌体和微小RNA(MiR)代表了可应用于肿瘤微环境中细胞介导药物递送的其他新工具。最近的研究表明,MiR在对脂肪组织驻留巨噬细胞的旁分泌作用中发挥重要作用,其失调与肥胖、糖尿病以及伤口等糖尿病并发症的发病机制有关。脂肪组织中存在大量MiR,积极参与局部组织中脂肪生成、脂肪因子分泌、炎症和细胞间通讯的调节。这些结果为脂肪细胞分泌的外泌体微小RNA(A-SE-MiR)的功能提供了重要见解,并建议评估A-SE-MiR在肿瘤进展中的潜在作用、ASCs与癌细胞相互作用的潜在机制以及基于ASCs的治疗方法的临床安全性。