Role of hyaluronic acid on bone destruction and pulmonary metastasis in tumors

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 07671633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kurume University
• Principal Investigator: KOMIYA Setsuro Kurume Univ. School of Med. Lecturer, 医学部, 講師 (30178371)
• Co-Investigator(Kenkyū-buntansha): MATSUURA Tsuyoshi Kurume Univ. School of Med. Fellow, 医学部, 助手 (80209494) ; KAKIZOE Mitsuo Kurume Univ. School of Med. Fellow, 医学部, 助手 (30233662) ; NARITA Shugo Kurume Univ. School of Med. Fellow, 医学部, 助手 (10237604)
• Project Period (FY): 1995 – 1996
• Keywords: hyaluronic acid / metastasismalignancy / CD44 / osteosarcoma / CD44

Research Abstract

Hyaluronic acid (HA), mainly present in joint cartilage, synovium, and joint fluid, is a principal ingridient of connective tissues. Tumors originating in these parts seem to destroy the connective tissues including HA.We therefore investigated the biological significance of HA in tumors of musculoskeletal systems. Serum was obtained from 125 patients with benign or malignant bone tumors, diagnoses of which were established by pathological examinations. Benign cases were seen in 58 patients, and malignant were in 67.43 out of 67 malignant cases had pulmonary metastatic lesions, and 24 had no metastasis. The measurement of serum HA was conducted by sandaich binding protein assay, and HA values were statistically analyzed to check the correlation with the liver function, kidney function, inflammatory signs, benign or malignancy, pulmonary metastasis. Since HA is metabolized and inactivated in the liver, and its dysfunction causes the high level of serum HA,patients with liver function were excluded from this study. The following factors were significantly correlated with high HA level ; malignancy (p=0.0001), pulmonary metastasis (p=0.0001), age (p=0.0001), ESR (p=0.085), BUN (p=0.0116), Ch-E (p=0.0169), AIP (p=0.023), CRP(p=0.0675). HA derived from the destruction of bone matrix by cancer-or sarcoma-invasion, from the pulmonary tissues destoyed by the metastasis of tumors to the lung, or from pleural fluid seemed to be the source of high level of serum HA.Malignant cases with high HA and almost in cachexy usually have liver and kidney dysfunction, and thus there seems to be the correlation between high HA lelels and liver and kidney dysfuction. Flowcytometric analysis of osteosarcoma cells showed that a certain number of the cell lines expressed high levels of CD44 which is a ligand of HA,indicating that phenotypic expression of osteosarcoma cells could be affected by HA.