Cytogenetic and molecular pathologic profiles of bone and soft tissue tumors, and their MMPs expression

骨和软组织肿瘤的细胞遗传学和分子病理学特征及其 MMP 表达

• 批准号: 15390119
• 负责人: IWASAKI Hiroshi
• 金额: $ 8.38万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390119/
• 关键词: Bone and soft tissue tumors; molecular genetics; chromosomal abnormalities; matrix metalloproteinases (MMPs); sarcoma-; emmprin; malignant peripheral nerve sheath; solid tumors tumors; 骨軟部腫瘍; Imatinib; siRNA; 細胞外マトリックス; MMP; MPNST; PDGFR; 染

1) A new human cell line, FU-DDLS-1 established from a dedifferentiated liposarcoma exhibited immunopositive reaction for mdm2 and p53 proteins. Cytogenetically, FU-DDLS-1 displayed a hypertetraploid karyotype with giant marker chromosomes composed partly of chromosome 12 materials. CGH analysis demonstrated that a gain of 12q12-q21 detected in FU-DDLS-1 were essentially the same as those in the original sarcoma. The FU-DDLS-1 cell line may be a particularly useful model for studying the molecular pathogenesis of human dedifferentiated liposarcoma.2) cDNA microarray analysis of malignant peripheral nerve sheath tumors (MPNST) : Survivin and tenascin C expressions were upregulated in MPNST, validated by reverse transcription polymerase chain reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the protein level in six of eight cases compared with benign tumours. Tenascin C was also expressed at the invasive front and tumorous stroma in all MPNST cases. Survivin … More and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.3) Expression of emmprin and matrix metalloproteinases (MMPs) in peripheral nerve sheath tumors (PNSTs) : We found that emmprin and MT1-MMP may be malignant potential-related proteins in PNSTs, and that MMP-1 and 9 may help differentiation between schwannoma and neurofibroma, especially in their plexiform types. The expression patterns of MMP-1 and gelatinase B (MMP-9) could divide PNSTs into two groups : schwannoma versus neurofibroma/malignant PNST (MPNST). Higher expression levels (>3+) of MMP-9 were observed in 50% of schwannomas versus none in neurofibromas and MPNSTs, while those of MMP-1 were found in 35.7% of neurofibromas and 66.7% of MPNSTs versus none in schwannomas. RECK was the main inhibitor expressed in these 3 tumors, with no significant differences.4) Epithelioid sarcoma (ES) cell lines showed that they express emmprin, and co-culture of these ES cells with dermal fibroblasts resulted in upregulation of gelatinase A (MMP-2) in fibroblasts. This stimulation was inhibited by an activity-blocking peptide against emmprin and by antiemmprin antibody. Immunohistochemical analysis of 5 ES patient cases demonstrated diffuse emmprin expression in ES cells and MMP-2 expression in both ES cells and peritumoral fibroblasts. Soluble full-length emmprin released from ES cells was shown to stimulate MMP-2 production by fibroblasts. In conclusion, emmprin is expressed in ES in both membrane and soluble forms and stimulates MMP-2 production via interactions with fibroblasts, which could play a role in ES cell stromal invasion and vascular involvement. Less

1）一种新的人类细胞系，是由专用脂肪肉瘤建立的FU-DDLS-1，暴露于MDM2和P53蛋白的免疫阳性反应。从细胞遗传学上，FU-DDLS-1显示了一种高二倍体核型，其中一部分由12个染色体材料组成的巨型标记染色体。 CGH分析表明，在FU-DDLS-1中检测到的12q12-Q21的增益与原始肉瘤中的增益基本相同。 FU-DDLS-1细胞系可能是研究人类去分化的脂肪肉瘤的分子发病机理的特别有用的模型。2）cDNA微阵列分析恶性周围神经鞘肿瘤（MPNST）：survivin和tenascin c表达在MPNST中更新，MPNST中有验证的Prolymasesase Polymersase Prolymersarse Rections在MPNST中更新。免疫组织化学证实，在所有MPN病例中，在侵袭性的前沿和肿瘤基质中也表达了八例蛋白质水平中的Survivin在蛋白质水平上的Survivin上调。 Survivin … More and tenascin C may be associated with the malignant potential of MPNST and could be considered as potential therapeutic targets.3) Expression of emmmprin and matrix metalloproteinases (MMPs) in peripheral nerve sheath tumors (PNSTs) : We found that emmmprin and MT1-MMP may be malignant potential-related proteins in PNSTs, and that MMP-1 and 9 may有助于分化切旺纳马瘤和神经纤维瘤，尤其是在其丛状类型中。 MMP-1和明胶酶B（MMP-9）的表达模式可以将PNST分为两组：Schwannoma与神经纤维瘤/恶性PNST（MPNST）。在50％的Schwannomas中观察到MMP-9的较高表达水平（> 3+），而在神经纤维瘤和MPNST中则观察到了较高的表达水平，而在35.7％的神经纤维瘤中发现了MMP-1，而MMP-1的MMP-1则在Schwannomas中观察到35.7％的神经纤维瘤和66.7％的MPNST。 RECK是在这3个肿瘤中表达的主要抑制剂，没有显着差异。4）上皮细胞肉瘤（ES）细胞系表明它们表达EMMMPRIN，并且这些ES细胞与真皮成纤维细胞的共培养导致胶质细胞中胶质素酶A（MMP-2）的上调。这种刺激受到对EMMMPRIN和抗EMMMPRIN抗体的活性阻断肽的抑制。对5例患者病例的免疫组织化学分析表明，ES细胞中ES细胞中的EMMMPRIN表达和MMP-2表达在ES细胞和周围成纤维细胞中均表达。显示从ES细胞释放的可溶性全长EMMMPRIN可通过成纤维细胞刺激MMP-2的产生。总之，EMMMPRIN以ES在膜和固体形式中表达，并通过与成纤维细胞相互作用刺激MMP-2产生，这可能在ES细胞基质侵袭和血管参与中起作用。较少的

项目成果

Chromosomal imbalances in angioleiomyomas by comparative genomichybridization

通过比较基因组杂交研究血管平滑肌瘤的染色体失衡

• 发表时间: 2004
• 期刊: Int J Mol Med 13(1)
• 作者: Nishio J;Iwasaki H;et al.
• 通讯作者: et al.

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization.

后纵隔炎性肌纤维母细胞瘤：使用免疫组织化学和荧光原位杂交测定的一例患有间变性淋巴瘤激酶异常的老年病例。

• 发表时间: 2005
• 期刊: Virchows Arch 446(4)
• 作者: Nishimura;N. et al.;Akimoto Y et al.
• 通讯作者: Akimoto Y et al.

Nishio J, Iwasaki H, et al.: "Establishment of a novel human dedifferentiated liposarcoma cell line, FU-DDLS-1 : conventional and molecular cytogenetic characterization"Int J Oncol. 22(3). 535-542 (2003)

Nishio J、Iwasaki H 等人：“新型人去分化脂肪肉瘤细胞系 FU-DDLS-1 的建立：常规和分子细胞遗传学表征”Int J Oncol。

Nishio J, Iwasaki H, et al.: "Chromosomal imbalances in angioleiomyomas by comparative genomic hybridization"Int J Mol Med. 13(1). 13-16 (2004)

Nishio J、Iwasaki H 等人：“通过比较基因组杂交研究血管平滑肌瘤中的染色体失衡”Int J Mol Med。

Establishment and characterization of a novel myxofibrosarcoma cell line

• DOI: 10.1016/j.cancergencyto.2005.02.003
• 发表时间: 2005-08-01
• 期刊: CANCER GENETICS AND CYTOGENETICS
• 作者: Kawashima, H;Ogose, A;Endo, N
• 通讯作者: Endo, N