gC1qR/HABP1/p32 is a potential new therapeutic target against mesothelioma Journal Article
| Authors: | Peerschke, E.; Stier, K.; Li, X.; Kandov, E.; de Stanchina, E.; Chang, Q.; Xiong, Y.; Manova-Todorova, K.; Fan, N.; Barlas, A.; Ghebrehiwet, B.; Adusumilli, P. S. |
| Article Title: | gC1qR/HABP1/p32 is a potential new therapeutic target against mesothelioma |
| Abstract: | Mesothelioma is an aggressive cancer of the serous membranes with poor prognosis despite combination therapy consisting of surgery, radiotherapy, and platinum-based chemotherapy. Targeted therapies, including immunotherapies, have reported limited success, suggesting the need for additional therapeutic targets. This study investigates a potential new therapeutic target, gC1qR/HABP1/p32 (gC1qR), which is overexpressed in all morphologic subtypes of mesothelioma. gC1qR is a complement receptor that is associated with several cellular functions, including cell proliferation and angiogenesis. In vitro and in vivo experiments were conducted to test the hypothesis that targeting gC1qR with a specific gC1qR monoclonal antibody 60.11 reduces mesothelioma tumor growth, using the biphasic mesothelioma cell line MSTO-211H (MSTO). In vitro studies demonstrate cell surface and extracellular gC1qR expression by MSTO cells, and a modest 25.3 ± 1.8% (n = 4) reduction in cell proliferation by the gC1qR blocking 60.11 antibody. This inhibition was specific for targeting the C1q binding domain of gC1qR at aa 76–93, as a separate monoclonal antibody 74.5.2, directed against amino acids 204–218, had no discernable effect. In vivo studies, using a murine orthotopic xenotransplant model, demonstrated an even greater reduction in MSTO tumor growth (50% inhibition) in mice treated with the 60.11 antibody compared to controls. Immunohistochemical studies of resected tumors revealed increased cellular apoptosis by caspase 3 and TUNEL staining, in 60.11 treated tumors compared to controls, as well as impaired angiogenesis by decreased CD31 staining. Taken together, these data identify gC1qR as a potential new therapeutic target against mesothelioma with both antiproliferative and antiangiogenic properties. © Copyright © 2020 Peerschke, Stier, Li, Kandov, de Stanchina, Chang, Xiong, Manova-Todorova, Fan, Barlas, Ghebrehiwet and Adusumilli. |
| Keywords: | mesothelioma; therapeutic target; complement; monoclonal antibody therapy; gc1qr/habp1/p32 |
| Journal Title: | Frontiers in Oncology |
| Volume: | 10 |
| ISSN: | 2234-943X |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2020-08-12 |
| Start Page: | 1413 |
| Language: | English |
| DOI: | 10.3389/fonc.2020.01413 |
| PROVIDER: | scopus |
| PMCID: | PMC7435067 |
| PUBMED: | 32903438 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
35Barlas -
161Manova-Todorova -
36Chang -
343De Stanchina -
496Adusumilli -
18Fan -
55Peerschke -
9Li -
5Xiong
Related MSK Work