Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance.
Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance.
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DOI：
10.3390/ijms19010311
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发表时间：
2018-01-21
影响因子：
5.6
通讯作者：
Rolauffs B
中科院分区：
文献类型：
--
作者：
Boehme KA;Schleicher SB;Traub F;Rolauffs B
与其他恶性骨肿瘤不同，包括骨肉瘤和尤文肉瘤，其发病率在青少年和年轻人中达到高峰，传统和去分化软骨肉瘤主要影响4th至7th十年的人。迄今为止，软骨肉瘤起源的细胞类型尚未明确定义。然而，似乎骨髓中的间充质干细胞和祖细胞（MSPC）面临着促增殖以及主要的软骨形成分化环境，如在该年龄的早期骨关节炎（OA）中所涉及的，是软骨肉瘤发生的来源。但是MSPC怎么会变成恶性的呢？事实上，每100万人中只有一人会发展成软骨肉瘤，而OA的发病率要高出一千倍。这意味着一个罕见的巧合的因素，允许逃避衰老和细胞凋亡，以及诱导血管生成和迁移，需要产生软骨肉瘤。在早期阶段，软骨肉瘤仍然被认为是一种很少转移的中间型肿瘤。不幸的是，晚期显示出对化疗和放疗的明显抵抗，并且经常转移。在这篇综述中，我们阐明了与软骨肉瘤的发生和治疗耐药性相关的信号通路，重点关注MSPC与关节软骨（AC）中的信号通路。
Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC).
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作者：
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