RELATIONSHIP BETWEEN SERUM CONCENTRATIONS OF THE GROWTH-FACTOR PLEIOTROPHIN AND PLEIOTROPHIN POSITIVE TUMORS

Background: Growth factors produced by tumor cells are essential for t umor expansion and may be useful in monitoring tumor progression or th erapeutic efficacy if the factors are released into the circulation. I n this study, we measured serum levels of pleiotrophin, a secreted hep arin-binding growth and angiogenesis factor, in mice bearing human tum or xenografts to determine whether these levels reflected overall tumo r burden, and we examined the relationship between tumor expression of pleiotrophin and serum levels of this factor in patients with cancer, Methods: Pleiotrophin in serum from mice and humans was measured by u se of a highly sensitive enzyme-linked immunosorbent assay. For the cl inical studies, serum specimens were obtained from 193 patients with v arious cancers of the gastrointestinal tract and from 28 healthy contr ol subjects, In a subset of 64 cancer patients, serum levels of pleiot rophin were measured at the time of surgery, and tumor expression of t his factor was detected immunohistochemically. Ail P values are two-si ded. Results: In mice, serum pleiotrophin levels were found to increas e as a function of tumor size. In humans, elevated serum pleiotrophin levels were found in patients with pancreatic cancer (n = 41; P<.0001) and colon cancer (n = 65; P =.0079) but not in patients with stomach cancer (n = 87; P =.42). A statistically significant positive associat ion was found between elevated levels of pleiotrophin in serum drawn a t the time of surgery and expression of this factor by tumors (P<.0001 ). In both mice and humans, serum pleiotrophin levels dropped after su ccessful tumor removal. Conclusions: Elevated serum pleiotrophin level s can indicate the presence of tumors expressing this factor, Monitori ng serum levels of pleiotrophin may prove useful in determining the ph armacologic efficacy of cytotoxic or anti-pleiotrophin therapy.