Bentel J M, Rhodes G C, Markus I, Smith G J
Carcinogenesis Research Unit, (School of Pathology), University of N.S.W. Kensington, Australia.
Int J Cancer. 1990 Aug 15;46(2):251-7. doi: 10.1002/ijc.2910460218.
Several passage cycles of poorly metastatic malignant epithelial cells through immunosuppressed mice failed to induce enhanced metastasis-forming ability of cells derived from either the primary subcutaneous tumours or the resultant lung metastases. In vitro treatment of cultured malignant cells with dimethyl sulphoxide (DMSO) induced a reversible change in phenotype towards increased invasiveness but did not significantly increase metastasis formation. A cloned-cell line from a spontaneous in vitro transformant in the presence of DMSO was highly invasive and highly metastatic. In vitro treatment of cultured cells with 2% (v/v) DMSO produced alterations in morphology with decreased growth rate of all cell lines and decreased anchorage-independent colony formation in several malignant cell lines. All in vitro and in vivo effects were reversible following both short- and long-term (1 year) culture of cells in the presence of DMSO, suggesting epigenetic effects. These data support the concept of independent genetic controls for the invasiveness of tumours and the ability to form metastases.
低转移性恶性上皮细胞在免疫抑制小鼠体内经过几个传代周期,未能诱导出源自原发性皮下肿瘤或由此产生的肺转移瘤的细胞形成转移的能力增强。用二甲基亚砜(DMSO)对培养的恶性细胞进行体外处理,可诱导表型发生可逆变化,使其侵袭性增加,但并未显著增加转移的形成。在DMSO存在下,从自发体外转化体获得的克隆细胞系具有高度侵袭性和高转移性。用2%(v/v)DMSO对培养细胞进行体外处理,会导致形态改变,所有细胞系的生长速率降低,几种恶性细胞系中不依赖贴壁的集落形成减少。在DMSO存在下对细胞进行短期和长期(1年)培养后,所有体外和体内效应都是可逆的,提示存在表观遗传效应。这些数据支持肿瘤侵袭性和形成转移能力受独立遗传控制的概念。