Recombinant CBD-HepII polypeptide of fibronectin inhibits alphavbeta3 signaling and hematogenous metastasis of tumor.
The interaction of integrin alphavbeta3 and its ligands are crucial for tumor metastasis. Recombinant CBD-HepII polypeptide of fibronectin, designated as CH50, suppressed the binding of tumor cells to ECM molecules, and abolished the promoting effect of soluble fibronectin and fibrinogen on tumor cell adhesion to ECM molecules. The underlying mechanisms involve the blockade and downregulation of alphavbeta3 and its co-receptor syndecan 1 by CH50. The activation of FAK, upregulation of cdc2, the production and activation of MMP-2 and MMP-9 by ECM molecules-stimulated tumor cells were inhibited by CH50. CH50 reduced the tumor cell arrest during blood flow, and also inhibited the invasive ability of tumor cells. The in vivo expressed CH50 suppressed the lung metastasis of circulating tumor cells, and prolonged the survival of mice after tumor cell inoculation. These findings suggest a prospective utility of CH50 in the gene therapy for prevention of tumor metastasis.
Gong
Wei
W
Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, People's Republic of China.
Liu
Yi
Y
Huang
Bo
B
Lei
Zhang
Z
Wu
Feng-Hua
FH
Li
Dong
D
Feng
Zuo-Hua
ZH
Zhang
Gui-Mei
GM
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology / Q000627:therapeutic use*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015316:Genetic Therapy; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D015996:Survival Rate
C478562:CH50 recombinant polypeptide; D005353:Fibronectins; D039302:Integrin alphaVbeta3; D011994:Recombinant Proteins; D005340:Fibrinogen; D051417:Focal Adhesion Kinase 1; D016203:CDC2 Protein Kinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9