Retinoblastoma (RB) is the most common primary eye cancer in children and an important clinical problem facing ocular oncologists. One present challenge in the treatment of retinoblastoma is the incidence of metastatic or secondary tumors that reduce life span and quality of survival. Those who survive RB are at increased risk for developing additional malignancies.
Our lab has identified cells in retinoblastoma that behave as tumor-initiating cells and are thought to be responsible for both tumor invasion and resistance to chemotherapy drugs. We also have found that these same tumor stem-like cells co-express adhesive molecules that may aid in metastasis, leading to new tumors at distant sites in the body. In collaboration with our colleagues at Cornell University, we seek to understand how these tumor stem cells invade tissues, as well as potential ways to block tumor spread. In order to eliminate these tumor-initiating RB cells, we are working with colleagues at Harvard University to immunologically target RB tumor-initiating cells for destruction. These multidisciplinary and collaborative approaches will allow us to understand both the metastatic mechanism(s) of RB tumor stem cells, as well as the potential means to eliminate these cells in a meaningful, therapeutic way.
Seigel, GM. 2011. Differentiation potential of human retinoblastoma cells. Curr. Pharm. Biotechnology Feb 1;12(2):213-6. PMID: 21044005
Li X, Pan YZ, Seigel GM, Hu ZH, Huang M, Yu AM. 2011. Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, -519c and -520h) and their differential expression in stem-like ABCG2+ cancer cells, Biochemical Pharmacology, Mar 15;81(6):783-92. PMID: 21219875
Cassidy L, Bejjani A, Choi MR and Seigel GM. 2012. Comparison of mature retinal marker expression in Y79 and WERI-RB27 human retinoblastoma cell lines, Oncocytology 2:1-5. PMID pending.
Bejjani A, Choi M, Cassidy L, Ksander B, O’Brien J, Murray T and Seigel GM. 2012. RB116: An RB+ retinoblastoma cell line expressing primitive markers, Molecular Vision. 18:2805-13. Epub 2012 Nov 29. PMID: 23233783 [PubMed - in process]
Silva AK, Yi H, Hayes SH, Seigel GM, Hackam AS. Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines: a potential role for the canonical Wnt signaling pathway. Mol Vis. 2010 Jan 13;16:36-45.
Kelly JP, Weiss AH, Rowell G, Seigel GM. Autofluorescence and infrared retinal imaging in patients and obligate carriers with neuronal ceroid lipofuscinosis. Ophthalmic Genet. 2009 Dec;30(4):190-8.
Hayes SH, Seigel GM. Immunoreactivity of ICAM-1 in human tumors, metastases and normal tissues. Int J Clin Exp Pathol. 2009 Jun 10;2(6):553-60.
Magupalli VG, Schwarz K, Alpadi K, Natarajan S, Seigel GM, Schmitz F. Multiple RIBEYE-RIBEYE interactions create a dynamic scaffold for the formation of synaptic ribbons. J Neurosci. 2008 Aug 6;28(32):7954-67.
Alpadi K, Magupalli VG, Koppel S, Koblitz L, Schwarz K, Seigel GM, Sung CH, Schmitz F. RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses. J Biol Chem. 2008 Sep 26;283(39):26461-7. Epub 2008 Jul 29.
Seigel GM, Hackam AS, Ganguly A, Mandell LM, Gonzalez-Fernandez F. Human embryonic and neuronal stem cell markers in retinoblastoma. Mol Vis. 2007 Jun 8;13:823-32.
Neekhra A, Luthra S, Chwa M, Seigel G, Gramajo AL, Kuppermann BD, Kenney MC. Caspase-8, -12, and -3 activation by 7-ketocholesterol in retinal neurosensory cells. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1362-7.
Seigel GM, Lupien SB, Campbell LM, Ishii DN. Systemic IGF-I treatment inhibits cell death in diabetic rat retina. J Diabetes Complications. 2006 May-Jun;20(3):196-204.
Nakanishi Y, Nakamura M, Mukuno H, Kanamori A, Seigel GM, Negi A. Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase. Exp Eye Res. 2006 Nov;83(5):1108-17. Epub 2006 Jul 12.
Narayanan R, Mungcal JK, Kenney MC, Seigel GM, Kuppermann BD. Toxicity of triamcinolone acetonide on retinal neurosensory and pigment epithelial cells. Invest Ophthalmol Vis Sci. 2006 Feb;47(2):722-8.
Luthra S, Narayanan R, Marques LE, Chwa M, Kim DW, Dong J, Seigel GM, Neekhra A, Gramajo AL, Brown DJ, Kenney MC, Kuppermann BD. Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosensory retinal, and microvascular endothelial cells. Retina. 2006 May-Jun;26(5):512-8.
Seigel GM, Campbell LM, Narayan M, Gonzalez-Fernandez F. Cancer stem cell characteristics in retinoblastoma. Mol Vis. 2005 Sep 12;11:729-37.