Protein metabolism in human colon carcinomas: in vivo investigations using a modified tracer technique with L-[1-13C]leucine

To quantify the protein anabolism of tumors it is not sufficient simply to determine the level of protein synthesis. The decisive factor is the net balance. This is the first attempt to establish this parameter in human tumors in vivo. Intraoperative tumor leucine/protein metabolism was studied in 15 patients with resectable malignant colon tumors using a balance model and L[1-13C]leucine as the tracer substance. Comparative measurements were also carried out simultaneously for peripheral tissue (forearm); in addition, protein kinetics parameters were established for the whole body using a proven two-pool model (with the same tracer as above). In view of the frequently conflicting data on amino acid metabolism in tumors, the tumoral and peripheral exchange rates of 20 amino acids were also determined. In tumors, essential and branched-chain amino acid uptakes were found to be 1.68 +/- 0.59 (SE) and 1.52 +/- 0.23 mumol/100 g tissue/min, respectively; in peripheral tissue there was overall an amino acid release [-0.11 +/- 0.06 and -0.05 +/- 0.04 mumol/100 g/min; in either case P < 0.01 (tumor versus periphery)]. Tracer analyses yielded a net retention for the tumors but a protein loss for peripheral tissue (8.941 +/- 3.113 versus -0.557 +/- 0.53 g/kg/24 h; P < 0.01) and for the whole body (-0.363 +/- 0.04 g/kg/24 h). The tumors were divided into two prognostic groups on the basis of their histology. Significant differences were found between the two groups in terms of the net retention rate for 10 amino acids, including leucine; retention was elevated in tumors with an unfavorable prognosis, possibly due to a higher amino acid requirement because of more rapid growth or for export processes (mucus production). The protein balance model used here has proved satisfactory for our purposes and could also be used to directly evaluate dietary measures (e.g., adjuvant parenteral nutrition in connection with chemotherapy).