Department of Medicine, Division of Hematology/Oncology, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, USA.
Exp Hematol. 2011 Nov;39(11):1072-80. doi: 10.1016/j.exphem.2011.08.008. Epub 2011 Aug 22.
Microvesicles have been shown to mediate varieties of intercellular communication. Work in murine species has shown that lung-derived microvesicles can deliver mRNA, transcription factors, and microRNA to marrow cells and alter their phenotype. The present studies evaluated the capacity of excised human lung cancer cells to change the genetic phenotype of human marrow cells. We present the first studies on microvesicle production by excised cancers from human lung and the capacity of these microvesicles to alter the genetic phenotype of normal human marrow cells. We studied 12 cancers involving the lung and assessed nine lung-specific mRNA species (aquaporin, surfactant families, and clara cell-specific protein) in marrow cells exposed to tissue in co-culture, cultured in conditioned media, or exposed to isolated lung cancer-derived microvesicles. We assessed two or seven days of co-culture and marrow which was unseparated, separated by ficoll density gradient centrifugation or ammonium chloride lysis. Under these varying conditions, each cancer derived from lung mediated marrow expression of between one and seven lung-specific genes. Microvesicles were identified in the pellet of ultracentrifuged conditioned media and shown to enter marrow cells and induce lung-specific mRNA expression in marrow. A lung melanoma and a sarcoma also induced lung-specific mRNA in marrow cells. These data indicate that lung cancer cells may alter the genetic phenotype of normal cells and suggest that such perturbations might play a role in tumor progression, tumor recurrence, or metastases. They also suggest that the tissue environment may alter cancer cell gene expression.
微泡已被证明可以介导多种细胞间通讯。在鼠类物种中的研究表明，肺来源的微泡可以将 mRNA、转录因子和 microRNA 递送到骨髓细胞中，并改变其表型。本研究评估了切除的人类肺癌细胞改变人类骨髓细胞遗传表型的能力。我们首次研究了从人肺切除的癌症产生的微泡及其改变正常人类骨髓细胞遗传表型的能力。我们研究了 12 例涉及肺部的癌症，并评估了骨髓细胞中暴露于共培养组织、培养在条件培养基中或暴露于分离的肺癌衍生微泡的 9 种肺特异性 mRNA 种（水通道蛋白、表面活性剂家族和克拉拉细胞特异性蛋白）。我们评估了共培养 2 或 7 天以及未经分离、用 ficoll 密度梯度离心或氯化铵裂解分离的骨髓。在这些不同的条件下，每种源自肺的癌症都介导了骨髓中 1 到 7 种肺特异性基因的表达。在超速离心条件培养基的沉淀物中鉴定出微泡，并证明其进入骨髓细胞并诱导骨髓中肺特异性 mRNA 表达。肺黑色素瘤和肉瘤也诱导骨髓细胞中肺特异性 mRNA 的表达。这些数据表明肺癌细胞可能改变正常细胞的遗传表型，并提示这种干扰可能在肿瘤进展、肿瘤复发或转移中发挥作用。它们还表明组织环境可能改变癌细胞的基因表达。
