Two-dimensional total correlated proton nuclear magnetic resonance spectroscopy (TOCSY) at 600 MHz was used for an ex vivo biochemical analysis of a benign human smooth muscle tumor (leiomyoma) and high grade malignant smooth muscle tumor (leiomyosarcoma). While there are a number of applications of proton nuclear magnetic resonance magnitude-mode two-dimensional correlated spectroscopy (COSY) to the ex vivo study of tissues and cells in the literature, to our knowledge this is the first application of TOCSY for the ex vivo study of biological tissue. Comparison of TOCSY and purged COSY data demonstrate the potential sensitivity advantages of the TOCSY method for the study of heterogeneous biological tissues. These TOCSY spectra were used to identify and quantitate a wide range of metabolites such as amino acids, peptides, triglycerides, phospholipid precursors and degradation products, bound fucose, and other saccharides. The leiomyosarcoma was found to have 5-fold higher levels of triglycerides and a 7-fold increase in the glycerophospho-choline:choline ratio compared to the leiomyoma. These metabolite changes may enhance membrane fluidity in the leiomyosarcoma compared to leiomyoma and thus may be of fundamental importance to cell motility, recognition, sarcoma tumorigenesis, and metastatic potential.
Supported by Grants PRTF-00097-03 and EDT-82 from the American Cancer Society, The Brigham Surgical Group (all to S. S.), and NIH grant RR-00995. S. S. is the recipient of the American Cancer Society Career Development Award (Grant PRTF-00097-03).