Abstract PR03: Frizzled 9 expression is a potential marker of response to iloprost chemoprevention of lung cancer
| Autor: | Lori Nield, Meredith A. Tennis, Robert L. Keith, Daniel T. Merrick |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Frizzled Lung Cancer prevention business.industry respiratory system medicine.disease medicine.disease_cause Demethylating agent chemistry.chemical_compound medicine.anatomical_structure Oncology chemistry medicine Cancer research Lung cancer business Carcinogenesis Prostacyclin receptor Iloprost medicine.drug |
| Zdroj: | Cancer Prevention Research. 6:PR03-PR03 |
| ISSN: | 1940-6215 1940-6207 |
| Popis: | Lung cancer remains the leading cause of cancer death in the United States and chemoprevention offers an appealing area of investigation in the face of limited therapeutic success. We recently demonstrated improvement in endobronchial histology in former smokers after oral iloprost treatment. Of the 48 patients who received iloprost in the chemoprevention trial, 23 had regressive histology and 25 had stable or progressive histology. Identifying markers that predict response to treatment will refine target populations for future trials and clinical applications. In vitro studies of NSCLC indicate that iloprost, a prostacyclin analogue, acts through the G-protein coupled receptor Frizzled 9 (Fzd9) instead of the prostacyclin receptor. We hypothesize that Fzd9 expression status predicts response to iloprost chemoprevention and that expression is modified by promoter hypermethylation. Patients who have lost Fzd9 expression will not respond to iloprost treatment. If Fzd9 is lost by methylation, a demethylating agent could restore Fzd9 expression and sensitivity to iloprost chemoprevention. In a urethane A/J mouse model of lung cancer, Fzd9 mRNA expression is reduced in lung tumors compared to matched, uninvolved lung tissue. Human lung tumors demonstrated reduced Fzd9 mRNA expression compared to matched normal lung tissue. Fzd9 expression is also decreased in human primary dysplastic cell lines, suggesting that loss of Fzd9 expression occurs early in lung tumorigenesis. Non-transforming lung epithelial cell lines (B2B or HBEC) were treated for four weeks with 1% cigarette smoke condensate. B2B cells were treated with the tobacco carcinogen NNK (10μM) for 2 hours. Both treatment conditions resulted in reduced Fzd9 mRNA expression measured by qPCR. Future work will assess Fzd9 expression in an in vitro chemoprevention and smoking model, in tissues from additional mouse models of lung cancer, and in tissues from chemoprevention trials. These initial studies suggest that Fzd9 expression is lost in early smoking-induced lesions. This study has the potential to improve iloprost lung cancer chemoprevention by allowing future trials to more effectively target high-risk patients and by providing a clinical biomarker for identification of chemoprevention candidates. This abstract is also presented as Poster A29. Citation Format: Meredith Tennis, Lori Nield, Dan Merrick, Robert Keith. Frizzled 9 expression is a potential marker of response to iloprost chemoprevention of lung cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR03. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|