Professor, Departments of Surgery, Medicine & Oncology, McGill University and the McGill University Health Center
Royal Victoria Hospital
687 Pine Avenue West
Montreal, Quebec H3A 1A1
Tel.: 514-934-1934 ext. 36692 (Office); 514-934-1934 ext. 35772 (Laboratory)
pnina [dot] brodt [at] muhc [dot] mcgill [dot] ca (Email)
Expertise: Molecular aspects of cancer invasion and metastasis; Novel strategies for the prevention and treatment of cancer metastases
Summary of Research Activities
Dr. Brodt and her group are studying the molecular aspects of cancer metastasis. In particular, the roles of cell adhesion receptors, cytokines and growth factors in the regulation of angiogenesis, cancer cell invasion and metastasis. One project looks at the role of the type 1 Insulin-like growth factor receptor (IGF-1R) in metastasis and the signal transduction pathways involved in transcriptional regulation by IGF-IR, using a combination of approaches that include gene transfer, use of dominant negative mutants and promoter assays. The contribution of different receptor domains to the transcriptional regulation of different genes is also being investigated, as is the role of post- internalization receptor processing in trafficking and signaling.
Another area of interest to the group is gene therapy of cancer metastases. Multiple strategies are being developed for gene therapy of metastases based on the targeting and disruption of IGF-IR synthesis and/or signaling. These strategies are being tested in several cancer types including lung carcinomas, colorectal carcinomas, breast carcinomas and brain tumours.
Finally, Dr. Brodt and her team are also looking at the role of the host inflammatory response in liver metastasis. The molecular cascade that is initiated following tumour cell entry into the hepatic circulation is being investigated by a combination of in vivo and in vitro techniques. In particular, the role of cytokines such as TNF and IL-1 and of vascular endothelial adhesion receptors such as E-selectin, VCAM-1, PECAM-1 and ICAM-1 are being analysed using a combination of immunohistochemistry, fluorescence based techniques, molecular analyses and animal studies.
Auguste P, Fallavollita L, Wang N, Burnier J, Bikfalvi A, Brodt P. The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation. Am J Pathol. 2007 May;170(5):1781-92.
Yakar S, Nunez NP, Pennisi P, Brodt P, Sun H, Fallavollita L, Zhao H, Scavo L, Novosyadlyy R, Kurshan N, Stannard B, East-Palmer J, Smith NC, Perkins SN, Fuchs-Young R, Barrett JC, Hursting SD, LeRoith D. Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones. Endocrinology. 2006 Dec;147(12):5826-34. Epub 2006 Sep 7.
Samani AA, Yakar S, Leroith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007 Feb;28(1):20-47. Epub 2006 Aug 24 Jaalouk DE, Crosato M, Brodt P, Galipeau J. Inhibition of histone deacetylation in 293GPG packaging cell line improves the production of self-inactivating MLV-derived retroviral vectors. Virol J. 2006 Apr 7;3:27.
Wang N, Thuraisingam T, Fallavollita L, Ding A, Radzioch D, Brodt P. The secretory leukocyte protease inhibitor is a type 1 insulin-like growth factor receptor-regulated protein that protects against liver metastasis by attenuating the host proinflammatory response. Cancer Res. 2006 Mar 15;66(6):3062-70.