Tang Liu1,2,3,4, Zuyun Yan1, Yong Liu4, Edwin Choy3, Francis J Hornicek2, Henry Mankin3, Zhenfeng Duan2. 1. Department of Orthopedics, the 2nd Xiangya Hospital of Central South University, Changsha, China. 2. Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, David Geffen School of Medicine at University of Los Angeles, Los Angeles, California, USA. 3. Department of Orthopaedic surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 4. State Key Laboratory of Powder Metallurgy, Central South University, Changsha, China.
Abstract
BACKGROUND/AIMS: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. METHODS: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B) and further determined the functional effects of CD44 knockout in these cells. RESULTS: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. CONCLUSION: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients.
BACKGROUND/AIMS: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. METHODS: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic humanosteosarcoma cells (MNNG/HOS and 143B) and further determined the functional effects of CD44 knockout in these cells. RESULTS: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic humanosteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. CONCLUSION: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcomapatients.
Authors: Monserrat Gerardo-Ramírez; Friederike L Keggenhoff; Vanessa Giam; Diana Becker; Marco Groth; Nils Hartmann; Beate K Straub; Helen Morrison; Peter R Galle; Jens U Marquardt; Peter Herrlich; Monika Hartmann Journal: Int J Mol Sci Date: 2022-08-03 Impact factor: 6.208
Authors: Saied A Aboushanab; Vadim A Shevyrin; Grigory P Slesarev; Vsevolod V Melekhin; Anna V Shcheglova; Oleg G Makeev; Elena G Kovaleva; Ki Hyun Kim Journal: Plants (Basel) Date: 2022-03-10