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Growth Properties of Colonic Tumor Cells Are a Function of the Intrinsic Mitochondrial Membrane Potential

Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, New York

Requests for reprints: Barbara G. Heerdt, Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467. Phone: 718-920-2750; Fax: 718-882-4464; E-mail: heerdt{at}aecom.yu.edu.

Development of malignant transformation in the colonic mucosa includes disruption in the equilibrium between proliferation and apoptosis, decreased expression and deletions of the mitochondrial genome, alterations in mitochondrial enzymatic activity, and elevations in the mitochondrial membrane potential (m). Focusing on the role of the m in tumor development and progression, we generated novel isogenic colonic carcinoma cell lines that exhibit highly significant, stable differences in their intrinsic m. Using these cell lines, we have recently shown that the intrinsic m has a significant influence on steady state mitochondrial activity and the extent to which cells enter butyrate-mediated growth arrest and apoptotic cascades. Here, we report that the m is also profoundly linked to important tumorigenic properties of the cells. Compared with cells with lower m, cells with elevated intrinsic m have an enhanced capacity to (a) respond to hypoxia by avoiding apoptosis and initiating angiogenesis, (b) escape anoikis and grow under anchorage-independent conditions, and (c) invade the basement membrane. Combined with our previous work, these data implicate the intrinsic m of colonic carcinoma cells in determining the probability of tumor expansion and progression. (Cancer Res 2006; 66(3): 1591-6)