Mechanical strain and growth factors regulate expression of tenascin-C by OS cells additively.
Osteosarcoma (OS) is a kind of malignancy wherein the tumor cells form malignant bone-like or bone tissue. Tenascin-C (TN-C), an important extracellular matrix (ECM) protein, plays an indispensable role in tumor development. However, its regulatory factors, expression, and function in OS pathological process have not been studied extensively. Expression of TN-C is induced by growth factors as well as mechanical strain in fibroblast. So we asked whether mechanical stain and growth factors could induce TN-C expression in OS as well as which pathways were involved in those processes. We found that when mechanical strain was applied to OS cells cultured on silicone membrane, TN-C mRNA and protein levels were increased 10-fold within 8 h compared to the resting control. Likewise, when epidermal growth factors (EGFs) and insulin-like growth factor (IGF-1) were added to cells, TN-C mRNA levels increased six fold and eightfold, respectively, within 24h compared to the control. Growth factors (EGF and IGF-1) and mechanical strain had additive effects on the induction of TN-C mRNA expression in OS. Both ROCK-I/II inhibitor and MEK-1 inhibitor inhibited TN-C induction by EGF or IGF-1, while only ROCK-I/II inhibitor had a strong subdued effect on TN-C induction by mechanical strain. Taken together, our findings suggest that growth factors and mechanical strain can induce TN-C in OS through different pathways additively.
Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Yucal
Y
Wang
Yan
Y
Man
Yong
Y
Ding
Baoan
B
Ma
Xiuchun
X
Qiu
Qingyu
Q
Fan
Lianhe
L
Zheng
D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013002:Somatomedins / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D013002:Somatomedins; D019063:Tenascin; D004815:Epidermal Growth Factor; D054460:rho-Associated Kinases; D048369:MAP Kinase Kinase 1