Variations in contents of hyaluronan in the peritumoral micro-environment of human chondrosarcoma

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.