Abstract
Accurate prediction of tumor metastatic potential would be helpful in treatment planning and in the design of agents that modify the tumor phenotype. We report that three methods that are potentially transferable to the clinic – dynamic contrast enhanced MRI (DCE MRI), T1ρ-weighted imaging and low temperature fluorescence imaging (that could be performed on biopsy specimens) – distinguished between relatively indolent (A375P) and aggressive (C8161) metastatic human melanoma xenografts in nude mice, whereas T1 and T2 relaxation time measurements did not. DCE MRI data analyzed by the BOLus Enhanced Relaxation Overview (BOLERO) method in conjunction with concurrent measurements of the arterial input function yielded a blood transfer rate constant (Ktrans) which measures perfusion/permeability, that was significantly higher in the core of the indolent tumor than in the core of the aggressive tumor. Histological staining indicated that aggressive tumors had more blood vascular structure but fewer functional vascular structure than indolent tumors. Indolent tumors exhibited T1ρ values that were significantly higher than those of aggressive tumors at spin-locking frequencies >500Hz. The mitochondrial redox ratio, Fp/(Fp+NADH), where Fp and NADH are the fluorescence of oxidized flavoproteins and reduced pyridine nucleotides, respectively, of aggressive tumors was much higher (more oxidized) than that of indolent tumors and often showed a bimodal distribution with an oxidized core and a reduced rim. These differences observed between these two types of tumors, one indolent and one aggressive, if generalizable, would be very valuable in predicting human melanoma metastatic potential.
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References
Folberg R, Hendrix MJ & Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. American Journal of Pathology 156(2), 361-381 (2000).
Hendrix MJ, Seftor EA, Hess AR & Seftor RE. Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Nature Reviews Cancer 3(6), 411-421 (2003).
Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe’er J, Trent JM,Meltzer PS, Hendrix MJ. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. American Journal of Pathology 155(3), 739-752 (1999).
Maniotis AJ, Chen X, GArcia C, DeChristopher PS, Wu D, Pe’er J, Holberg R. Control of melanoma morphogenesis, endothelial survival, and perfusion by extracellular matrix. Laboratory Investigation 82(8), 1031-43 (2002).
Ruf W, Seftor EA, Petrovan RJ, Weiss RM, Gruman LM, Marganyan NV, Seftor EA, Nagle RB. Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Cancer Research 63(17), 5381-9 (2003).
Hendrix MJ, Seftor EA, Chu YW, Seftor RE, Magle RB. Coexpression of vimentin and keratins by human melanoma tumor cells: correlation with invasive and metastatic potential. Journal of the National Cancer Institute 84 (3), 165-174 (1992).
Welch DR, Bizi JE, Miller BE, Conoway D, Seftor EA, Yohan KH, Gilmore LB, Seftor RE, Nakajima M, Hendrix MJ. Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line. International Journal of Cancer 47 (2), 227-237 (1991).
Quistorff B, Haselgrove JC & Chance B. High resolution readout of 3-D metabolic organ structure: An automated, low-temperature redox ratio-scanning instrument. Anal. Biochem. 148389-400 (1985).
Kozlowski JM, Hart IR, Fidler IJ & Hanna N. A human melanoma line heterogeneous with respect to metastatic capacity in athymic nude mice. Journal of the National Cancer Institute 72 (4), 913-7 (1984).
Zhou R, Pickup S, Yankeelov TE, Springer CS & Glickson JD. Simultaneous measurement of arterial input function and tumor pharmacokinetics in mice by dynamic contrast enhanced imaging: effects of transcytolemmal water exchange. Magn. Reson. Med. 52248-57 (2004).
Yankeelov TE, Rooney WD, Li X & Springer CS Jr. Variation of the relaxographic "shutter-speed" for transcytolemmal water exchange affects the CR bolus-tracking curve shape. Magnetic Resonance in Medicine 50 (6), 1151-69 (2003).
Wheaton AJ, Borthakur A, Kneeland JB, Regatta RR, Akella SV, Reddy R. In vivo quantification of T1ρ using a multislice spin-lock pulse sequence. Magnetic Resonance in Medicine 52 (6), 1453-1458 (2004).
Borthakur A, Wheaton AJ, Gongontas AJ, Akella SV, Regatta RR, Charagundla SR, Reddy R. In vivo measurement of T1ρ dispersion in the human brain at 1.5 tesla. Journal of Magnetic Resonance Imaging 19 (4), 403-409 (2004).
Chance B, Schoener B, Oshino R, Itshak F & Nakase Y. Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. Journal of Biological Chemistry 254 (11), 4764-4771 (1979).
Chance B. in Flavins and Flavoproteins (ed. Slater, E. C.) 498-510 (Elsevier, Amsterdam, (1966).
Chance B & Baltscheffsky H. Respiratory Enzymes in Oxidative Phosphorylation. J. Biol. Chem. 233(2), 736-739 (1958).
Virta A, Komu M & Kormano M. T1rho of protein solutions at very low fields: dependence on molecular weight, concentration, and structure.Magnetic Resonance in Medicine 37(1), 53-57 (1997).
Duvvuri U, Golberg AD, Krantz JK, Hoang L, Reddy R, Wehrli FW, Wand AJ, Englander SW, Leigh JS. Water magnetic relaxation dispersion in biological systems: the contribution of proton exchange and implications for the noninvasive detection of cartilage degradation. Proceedings of the National Academy of Sciences of the United States of America 98(22), 12479-12484 (2001).
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Li, L.Z. et al. (2008). Predicting Melanoma Metastatic Potential By Optical And Magnetic Resonance Imaging. In: Maguire, D.J., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXVIII. Advances in Experimental Medicine and Biology, vol 599. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71764-7_10
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DOI: https://doi.org/10.1007/978-0-387-71764-7_10
Publisher Name: Springer, Boston, MA
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