Abstract 932: Wnt antagonist, secreted frizzled-related protein 4 (SFRP4) and peptides from its associated domains, increases chemotherapeutic response of cancer stem cells of malignant mesothelioma cell lines
Authors: Perumal Vanathi , Kumar Senthil , Arfuso Frank , Fox Simon , Dharmarajan Arunasalam 
Published: July 2017

Malignant mesothelioma (MM) is a highly aggressive cancer associated with past asbestos exposure that is characterized by rapid progression, late metastases and poor prognosis. There is a need for much improved and novel therapies for this cancer through improved biological understanding of the disease.Previous studies have shown that SFRPs in general and SFRP4 in particular are down regulated in mesothelioma tissue and cell lines 1-4. Based on our own study and previously demonstrated a role for sFRP4 in making chemoresistant tumours amenable to chemotherapeutics 5-16. We have now progressed our work into the effects of peptides derived from the cysteine-rich domain and the netrin-like domain of sFRP4 on tumour initiating cells derived from MM cell lines.We examined the effect of secreted frizzled-related protein 4 (sFRP4), a Wnt signaling antagonist and its associated peptides, in chemosensitizing the MM cell line ONE 58 and JU77 and MM cancer stem cells (CSCs) enriched from these two cell lines to chemotherapeutics.We found tumorspheres exposed to sFRP4 and peptides alone and in combination with cisplatin induced cell death and decreased CD133 and ALDH1 expression.We thus identified for the first time that sFRP4 and associated peptides could help to sensitise to chemotherapeutics and destroy cancer stem cells of MM cell line, which would lead to effective treatment regimen to combat malignant mesothelioma. Our initial in vitro data exemplify the ability of these peptides in diminishing the numbers of therapy-resistant Tumor initiating cells (TICs).

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Citation Format: Vanathi Perumal, Senthil Kumar, Frank Arfuso, Simon Fox, Arunasalam Dharmarajan. Wnt antagonist, secreted frizzled-related protein 4 (SFRP4) and peptides from its associated domains, increases chemotherapeutic response of cancer stem cells of malignant mesothelioma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 932. doi:10.1158/1538-7445.AM2017-932