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

1)人去分化脂肪肉瘤细胞系FU-DDLS-1对MDM2和P53蛋白呈免疫阳性反应。在细胞遗传学上，FU-DDLS-1表现为超四倍体核型，其巨型标记染色体部分由12号染色体材料组成。CGH分析表明，在FU-DDLS-1中检测到的12q12-q21的增益与原始肉瘤基本相同。FU-DDLS-1细胞系可能是研究人去分化脂肪肉瘤分子发病机制的一个特别有用的模型。2)恶性周围神经鞘瘤(MPNST)的基因芯片分析：逆转录聚合酶链式反应证实，Survivin和Tenascin C在MPNST中表达上调。免疫组织化学证实，与良性肿瘤相比，8例中有6例MPNST中Survivin蛋白表达上调。在所有MPNST病例中，Tenascin C在侵袭前沿和肿瘤间质中也有表达。Survivin…More和Tenascin C可能与MPNST的恶性潜能有关，可作为潜在的治疗靶点。3)emmprin和基质金属蛋白酶(MMPs)在周围神经鞘瘤(PNSTs)中的表达：我们发现在PNSTs中Emmprin和MT1-MMPs可能是恶性潜能相关蛋白，而MMP1和MMP9可能有助于区分神经鞘瘤和神经纤维瘤，尤其是在神经纤维瘤的丛状型。根据MMP1和明胶酶B(MMP9)的表达可将PNST分为神经鞘瘤组和神经纤维瘤/恶性PNST组(MPNST)。在神经纤维瘤和MPNSTs中有35.7%和66.7%的神经鞘瘤有较高的表达水平。4)上皮样肉瘤(ES)细胞株表达Emmprin，与真皮成纤维细胞共培养可诱导成纤维细胞表达明胶酶A(MMP2)。这种刺激可被针对Emmprin的活性阻断肽和抗Emmprin抗体所抑制。免疫组织化学染色显示5例ES患者的ES细胞表达弥漫性Emmprin蛋白，瘤周成纤维细胞和ES细胞均表达MMP2。ES细胞释放的可溶性全长Emmprin可刺激成纤维细胞产生基质金属蛋白酶-2。总之，Emmprin在ES细胞中以膜和可溶性的形式表达，并通过与成纤维细胞的相互作用刺激基质金属蛋白酶-2的产生，这可能在ES细胞的基质侵袭和血管侵犯中发挥作用。较少

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