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)从去分化脂肪肉瘤中建立的新的人细胞系FU-DDLS-1显示mdm 2和p53蛋白的免疫阳性反应。FU-DDLS-1的核型为超四倍体，标记染色体巨大，部分由12号染色体组成。CGH分析显示FU-DDLS-1中12 q12-q21的增加与原发肉瘤基本相同。FU-DDLS-1细胞系可能是研究人类去分化脂肪肉瘤分子发病机制的一个特别有用的模型。2）恶性外周神经鞘瘤（MPNST）的cDNA微阵列分析：Survivin和tenascin C在MPNST中表达上调，通过逆转录聚合酶链反应验证。免疫组化证实，与良性肿瘤相比，MPNST中有6例在蛋白水平上生存素表达上调。在所有MPNST病例中，Tenascin C也在浸润前沿和肿瘤间质中表达。Survivin ...更多信息 和腱生蛋白C可能与MPNST的恶性潜能有关，并可能被认为是潜在的治疗靶点。3）emmprin和基质金属蛋白酶（MMPs）在周围神经鞘瘤（PNST）中的表达：我们发现emmprin和MT 1-MMP可能是PNST恶性潜能相关蛋白，MMP-1和9可能有助于神经鞘瘤和神经纤维瘤的鉴别，尤其是丛状的MMP-1和明胶酶B（MMP-9）的表达模式可将PNST分为神经鞘瘤和神经纤维瘤/恶性PNST（MPNST）两组。MMP-9在50%的神经鞘瘤中的表达高于神经纤维瘤和MPNST，而MMP-1在35.7%的神经纤维瘤和66.7%的MPNST中的表达高于神经鞘瘤。RECK是这3种肿瘤中表达的主要抑制因子，差异无统计学意义。4）上皮样肉瘤（Epithelioid sarcoma，ES）细胞表达emmprin，ES细胞与真皮成纤维细胞共培养后，成纤维细胞中明胶酶A（gelatinase A，MMP-2）表达上调。这种刺激被抑制的活性阻断肽对emmprin和antiemmprin抗体。5例ES患者的免疫组化分析显示ES细胞中弥漫性emmprin表达，ES细胞和瘤周成纤维细胞中均表达MMP-2。从ES细胞释放的可溶性全长emmprin显示刺激成纤维细胞产生MMP-2。总之，emmprin在ES中以膜和可溶形式表达，并通过与成纤维细胞的相互作用刺激MMP-2的产生，这可能在ES细胞间质侵袭和血管受累中发挥作用。少

项目成果

Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

• DOI: 10.1038/modpathol.3800599
• 发表时间: 2006-06-01
• 期刊: MODERN PATHOLOGY
• 影响因子: 7.5
• 作者: Izumi, Teiyu;Oda, Yoshinao;Tsuneyoshi, Masazumi
• 通讯作者: Tsuneyoshi, Masazumi

Establishment and characterization of a renal cell carcinoma cell line (FU-UR-1) with the reciprocal ASPL-TFE3 fusion transcript.

具有相互 ASPL-TFE3 融合转录本的肾细胞癌细胞系 (FU-UR-1) 的建立和表征。

• 发表时间: 2004
• 期刊: Oncol Rep 11
• 作者: Ishiguro M;Iwasaki H;Ohjimi Y;Kaneko Y
• 通讯作者: Kaneko Y

Tumor budding in colorectal cancer. Chapter VIII : Cohort migration and IQGAP1

结直肠癌中的肿瘤出芽。

• 发表时间: 2006
• 作者: Nabeshima K;Iwasaki H;et al.
• 通讯作者: et al.

Nishio J, Iwasaki H, et al.: "Intra-abdominal small round cell tumour with EWS-WT1 fusion transcript in an elderly patient."Histopathology. 42(4). 410-412 (2003)

Nishio J、Iwasaki H 等人：“老年患者的腹内小圆细胞肿瘤，具有 EWS-WT1 融合转录本。”组织病理学。

Nabeshima K, et al.: "Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas"J Pathol. 202(3). 341-351 (2004)

Nabeshima K 等人：“Emmprin 是一种基质金属蛋白酶 (MMP) 的细胞表面诱导剂，在 T 细胞淋巴瘤中表达”J Pathol。