Anti-lipolysis-stimulated lipoprotein receptor monoclonal antibody as a novel therapeutic agent for endometrial cancer

Autor: Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Tatsuo Masuda, Mamoru Kakuda, Satoshi Nakagawa, Ai Miyoshi, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: BMC Cancer, Vol 22, Iss 1, Pp 1-12 (2022)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-022-09789-6
Popis: Abstract Background Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken–mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC. Methods We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro. Results High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35–9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p
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