Construction of a disulfide‐stabilized diabody against fibroblast growth factor‐2 and the inhibition activity in targeting breast cancer

Abstract

Fibroblast growth factor‐2 (FGF‐2) is one of the most important angiogenic factors to promote tumor growth, progression and metastasis. Neutralizing antibodies against FGF‐2 may suppress the growth of tumor cells by blocking the FGF‐2 signaling pathway. In this study, a disulfide‐stabilized diabody (ds‐Diabody) that specifically targets FGF‐2 was designed. Compared to its parent antibody, the introduction of disulphide bonds in the diabody could significantly increase the stability of ds‐Diabody and maintain its antigen binding activity. The ds‐Diabody against FGF‐2 could effectively inhibit the tube formation and migration of vascular endothelial cells and block the proliferation and invasion of human breast cancer cells. In the mouse model of breast cancer xenograft tumors, the ds‐Diabody against FGF‐2 could significantly inhibit the growth of tumor cells. Moreover, the densities of microvessels stained with CD31 and lymphatic vessels stained with LYVE1 in tumors showed a significant decrease following treatment with the ds‐Diabody against FGF‐2. Our data indicated that the ds‐Diabody against FGF‐2 could inhibit tumor angiogenesis, lymphangiogenesis and tumor growth.

Retracted: Blockade of ONECUT2 expression in ovarian cancer inhibited tumor cell proliferation, migration, invasion and angiogenesis

“…Tumor size was measured with a Vernier caliper every 3 days. Tumor volume was calculated using the formula V = 0.52ab 2 (a = tumor length; b = tumor width) . At the end of 21 days, nude mice were euthanized and tumors were stripped for immunohistochemistry assays.…”

“…Immunohistochemistry was carried out as previously described . The tumor tissue samples of ovarian cancer patients were provided by The Third Affiliated Hospital of Sun Yat‐sen University (Guangzhou, China).…”

“…mor width). 19 At the end of 21 days, nude mice were euthanized and tumors were stripped for immunohistochemistry assays.…”

“…Immunohistochemistry was carried out as previously described. 19,20 The tumor tissue samples of ovarian cancer patients were provided Technology), and rabbit anti-mouse ONECUT2 polyclonal antibody (1:500 dilution, ab28466; Abcam). The biotinylated HRP-conjugated secondary antibody was a goat anti-rabbit IgG.…”

Fibroblast growth factor�18 promotes the growth, migration and invasion of MDA‑MB‑231 cells

“…FGF1 could have an important role in human breast cancer growth and patients with high levels of bFGFR may have a more favorable prognosis ( 27 ). FGF2/FGFR interaction led to complex signal transduction pathways and to the activation of a ‘proangiogenic phenotype’ in the endothelium, which regulated the proliferation, migration and survival of breast cancer cells ( 28 ). The growth of lung and colon cancer cells were induced by the high expression of FGF18 ( 29 , 30 ) and FGF18 increased ovarian tumor growth and metastasis ( 14 ).…”