Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

Abstract

Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(−) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5±0.65 g) and an increased tumor volume (8.3±1.18 mm3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (214±9.8 ng/ml) and MMP9 (25.5±1.81 ng/ml) were higher in MT(+) group than in MT(−) group (165±7.8 ng/ml and 16.9±1.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells

“…In addition, silencing PREX2a expression suppressed OS cell proliferation, migration and invasion. MMP2 and MMP9 have been suggested to participate in the metastasis of OS (24), and the expression and activity of MMP2 and MMP9 are tightly associated with OS cell migration and invasion (25)(26)(27). The present study demonstrated that suppression of PREX2a notably inhibited the invasion and migration of OS cells, at least partly via suppressing the protein expression of MMP2 and MMP9.…”

Identification of Lysosome‐Associated Protein Transmembrane‐4 as a Novel Therapeutic Target for Osteosarcoma Treatment

“…Up to now, the pathogenesis and tumor driver genes of osteosarcoma have not been clarified, and the main treatment for osteosarcoma is surgery, chemotherapy, and adjuvant chemotherapy 22 . However, 40% of patients with osteosarcoma are at risk of pulmonary metastasis and recurrence, with a 5-year survival rate of only 20% 23,24 . Therefore, target therapy is a promising clinical treatment for osteosarcoma 25 .…”

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology

“…More recently, the presence of labeled epithelial cells in sentinel axillary nodes in patients with breast cancer was found to be increased in patients who underwent breast massage prior to the procedure (60). Although this was interpreted as a form of "benign mechanical transport," similar to that occurring with needle biopsies, rather than true micrometastases (61), there is a remaining debate on the long-term risks associated with such findings (62,63). There is also controversy over the role and safety of manual therapies and acupuncture in the management of lymphedema postcancer treatment (64,65).…”