Assessment of human colon cancer protein kinetics in vivo

Background. Malignancies enlarge because protein synthesis exceeds the rate of breakdown; however the specific protein kinetic pattern remains unknown. Determining in vivo protein kinetic rates for a tumor may be useful for quantifying individual responses to a specific therapy. The aim of this study was to assess whether the growth of tumors is related to an increase in protein synthesis or an inhibition of protein breakdown. Methods. Five patients (age, 59 ± 3 years) with adenocarcinoma of the colon undergoing colonoscopy were studied. Tissue protein synthesis and breakdown rates were measured in vivo for both segments of colon cancer and adjacent normal- appearing colonic mucosa by using a primed, continuous infusion of 1¹³C leucine with tissue biopsy and quantitation of regional blood flow by laser Doppler flowmetry. Results. Segments of colon cancer had a significantly (p < 0.05) greater rate of protein synthesis as quantitated by both the fractional rate of protein synthesis (Ca 45.4% ± 5.0%/day versus nl mucosa 35.7% ± 3.1%/day; mean ± SEM) and by the tissue synthesis rate (Ca 69.4 ± 9. 0 versus nl mucosa 51.6 ± 5.2 μmol/L leucine/day/100 gm tissue). Regional blood flow was significantly elevated in the cancer (Ca 110.9 ± 5.8 versus nl mucosa 91.2 ± 2.9 ml/min/100 gm), which contributed to commensurate rates of tissue breakdown (Ca 28.6 ± 2.0 versus nl mucosa 28.2 ± 2.4 μmol/L leucine/day/100 gm). Conclusions. These results illustrate that human colon cancers grow in vivo as a result of increases in protein synthesis. Furthermore, increases in regional blood flow limit the rate of tissue protein breakdown of colon cancer, thereby contributing to growth of the malignancy. These findings support the contention that therapeutic strategies aimed at negating this inherent increase in protein synthesis or limiting blood flow may effectively limit the growth of malignancies. This methodology may also provide an index for evaluating the effectiveness of future therapies aimed at reducing tumor growth for individual patients.