Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer
Journal
Cancer Science
Journal Volume
111
Journal Issue
10
Pages
3478-3492
Date Issued
2020
Author(s)
Abstract
Ovarian cancer has a high recurrence rate after platinum-based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer-specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV-3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross-reactivity to normal cells. Among these mAbs, OV-Ab 30-7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV-Ab 30-7 impaired laminin-induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor-bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV-Ab 30-7, may be considered as a potential therapeutic for ovarian cancer. ? 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association
Subjects
cell apoptosis; focal adhesion kinase; integrin α3; laminin; monoclonal antibody; ovarian cancer
SDGs
Other Subjects
alpha3 integrin; carboplatin; focal adhesion kinase; laminin; monoclonal antibody; ov ab 307; paclitaxel; protein p21; protein p53; unclassified drug; alpha3 integrin; carboplatin; cyclin dependent kinase inhibitor 1A; monoclonal antibody; paclitaxel; protein p53; animal experiment; animal model; apoptosis; Article; cancer inhibition; cancer prognosis; controlled study; drug protein binding; enzyme phosphorylation; female; human; human cell; immunohistochemistry; mouse; nonhuman; ovary cancer; priority journal; SK-OV-3 cell line; upregulation; animal; Bagg albino mouse; carcinoma; cell line; disease model; drug effect; HCT 116 cell line; metabolism; ovary tumor; pathology; prognosis; tumor cell culture; tumor recurrence; umbilical vein endothelial cell; Animals; Antibodies, Monoclonal; Apoptosis; Carboplatin; Carcinoma; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; Disease Models, Animal; Female; HCT116 Cells; Human Umbilical Vein Endothelial Cells; Humans; Integrin alpha3; Mice; Mice, Inbred BALB C; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Prognosis; Tumor Cells, Cultured; Tumor Suppressor Protein p53
Publisher
Blackwell Publishing Ltd
Type
journal article