Department of Neuroscience, Anatomy Institute, University of Padova, via Gabelli 65, Padova 35121, Italy.
Department of Orthopedics and Orthopedic Oncology, University of Padova, via Giustiniani 2, Padova 35121, Italy.
J Orthop Res. 2019 Feb;37(2):503-509. doi: 10.1002/jor.24176. Epub 2018 Dec 4.
A concept consolidated in recent years is that tumor growth depends to a great extent on the micro-environment surrounding the tumor, which has a fundamental role in tumor progression and in determining the effectiveness of therapies. Our analysis focuses on chondrosarcoma, the second primary malignant bone tumor, resistant to both chemotherapeutic and radiation therapy. We quantified hyaluronan, one of the main components of the extracellular matrix, with the aim of comparing its amount in the connective tissue surrounding the tumor with intra-tumoral tissue and healthy fascia of the same anatomic district, viewed as a health control. We demonstrate that hyaluronan increased significantly in the peritumoral stroma compared with the healthy fascia, which showed an average amount according to the physical characteristics of body districts by a mean value of 26.9 μg/g. In the peritumoral stroma, the mean hyaluronan content reached 132.6 μg/g (mean value of 63.2 μg/g). The p-value was less than 0.01, showing a highly significant statistical difference. Surprisingly, no significant differences were detected as a function of age, gender, or tumor grade. The levels of hyaluronan were comparable in peritumoral and tumor tissues, although there were differences depending on the state of necrosis. In addition, data on the expression of hyaluronic acid synthetase showed a decrease of about 50% in peritumoral and tumor tissues, indicating alterations in hyaluronan turnover and synthesis. This work demonstrates a variation in hyaluronan contents around the chondrosarcoma, likely correlated with the aggressiveness and resistance to chemotherapy of this tumors. Statement of Clinical Significance: Deeper knowledge about the composition of the peritumoral stroma, rich in extracellular matrix, will enhance better study and understanding of the metastatic potential of tumors and their prognostic indices. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:503-509, 2019.
近年来有一个概念得到了巩固，即肿瘤的生长在很大程度上依赖于肿瘤周围的微环境，而微环境在肿瘤的进展以及确定治疗效果方面起着根本性的作用。我们的分析集中在软骨肉瘤上，这是第二种原发性恶性骨肿瘤，对化疗和放疗均有耐药性。我们对透明质酸进行了量化，透明质酸是细胞外基质的主要成分之一，目的是比较肿瘤周围结缔组织与肿瘤内组织和同一解剖区域的健康筋膜之间的含量。我们证明，与健康筋膜相比，肿瘤周围基质中的透明质酸显著增加，健康筋膜的含量根据身体部位的物理特征呈平均水平，平均值为 26.9μg/g。在肿瘤周围基质中，透明质酸的平均含量达到 132.6μg/g（平均值为 63.2μg/g）。p 值小于 0.01，显示出高度显著的统计学差异。令人惊讶的是，透明质酸含量与年龄、性别或肿瘤分级无关，没有检测到显著差异。肿瘤周围和肿瘤组织中的透明质酸水平相当，尽管存在与坏死状态有关的差异。此外，关于透明质酸合成酶表达的数据显示，肿瘤周围和肿瘤组织中的表达降低了约 50%，表明透明质酸周转率和合成发生了改变。这项工作表明软骨肉瘤周围的透明质酸含量存在变化，这可能与这些肿瘤的侵袭性和对化疗的耐药性有关。临床意义声明：更深入地了解富含细胞外基质的肿瘤周围基质的组成，将有助于更好地研究和理解肿瘤的转移潜力及其预后指标。©2018 骨科研究协会。由 Wiley Periodicals，Inc. 出版。J Orthop Res 37:503-509，2019。
