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脂肪组织分泌的可溶性因子对增殖期和静止期骨肉瘤细胞的相反作用

Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells.

作者信息

Avril Pierre, Duteille Franck, Ridel Perrine, Heymann Marie-Françoise, De Pinieux Gonzague, Rédini Françoise, Blanchard Frédéric, Heymann Dominique, Trichet Valérie, Perrot Pierre

机构信息

Nantes and Tours, France From INSERM, UMR 957, Equipe Labellisée Ligue contre le Cancer 2012; the Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives; University Hospital, Service de Chirurgie Plastique et des Brûlés and Service d'Anatomie Pathologique; and University Hospital, Service d'Anatomie Pathologique.

出版信息

Plast Reconstr Surg. 2016 Mar;137(3):865-875. doi: 10.1097/01.prs.0000479989.88114.8b.

DOI:10.1097/01.prs.0000479989.88114.8b
PMID:26910666
Abstract

BACKGROUND

Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed.

METHODS

Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed.

RESULTS

Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres.

CONCLUSIONS

This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

摘要

背景

骨肉瘤是最常见的原发性骨恶性肿瘤(不包括骨髓瘤),切除术后可进行自体脂肪组织移植以满足美学需求。必须探讨自体脂肪组织移植在癌症复发潜在风险方面的安全性。

方法

在由MNNG-HOS细胞诱导的人骨肉瘤临床前模型中测试脂肪组织注射。用脂肪组织样本处理不含胎牛血清生长因子的培养基,并添加到两种骨肉瘤细胞系(MNNG-HOS和MG-63)中,这两种细胞系分别在单层培养或维持在非贴壁球体中,分别有利于增殖或静止阶段。分析增殖和细胞周期。

结果

脂肪组织注射增加了小鼠骨肉瘤的局部生长,但与肺转移或骨溶解的加重无关。脂肪组织衍生的可溶性因子使骨肉瘤细胞的体外增殖增加了180%。在脂肪组织条件培养基中测量的白细胞介素-6和瘦素浓度高于骨肉瘤细胞条件培养基中的浓度,但作者的结果表明它们并非单独起作用。此外,脂肪组织衍生的可溶性因子不利于非贴壁肿瘤球体中MNNG-HOS细胞从G0期到G1期的转变。

结论

本研究表明,脂肪组织可溶性因子激活骨肉瘤细胞周期从G1期到有丝分裂期,但不促进从静止的G0期到G1期的转变。自体脂肪组织移植可能不参与休眠肿瘤细胞或癌症干细胞的激活。

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