Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer

Autor: Kuan-Ting Kuo, Feng-Yi Ke, Yu-Chyi Hwang, Han-Chung Wu, Wan-Yu Chen, Ming-Chieh Lin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
endocrine system diseases
Integrin alpha3
Apoptosis
Carboplatin
chemistry.chemical_compound
Mice
0302 clinical medicine
Basic and Clinical Immunology
Ovarian carcinoma
Tumor Cells
Cultured
Ovarian Neoplasms
Mice
Inbred BALB C
biology
Antibodies
Monoclonal
General Medicine
Prognosis
female genital diseases and pregnancy complications
ovarian cancer
Oncology
030220 oncology & carcinogenesis
Immunohistochemistry
Original Article
Female
Antibody
Cyclin-Dependent Kinase Inhibitor p21
Paclitaxel
medicine.drug_class
Monoclonal antibody
Cell Line
03 medical and health sciences
laminin
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
cell apoptosis
integrin α3
business.industry
focal adhesion kinase
Carcinoma
medicine.disease
HCT116 Cells
Disease Models
Animal
030104 developmental biology
chemistry
Tumor progression
monoclonal antibody
Cancer cell
biology.protein
Cancer research
Neoplasm Recurrence
Local
Tumor Suppressor Protein p53
Ovarian cancer
business
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: 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.
The novel mAb, OV‐Ab 30‐7, can induce ovarian cancer cell apoptosis, and blockage integrin‐laminin signaling, and may be considered as a potential therapeutic for ovarian cancer.
Databáze: OpenAIRE
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