TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) PRODUCED IN TUMOR-TISSUE AFTER CHEMOTHERAPY ACTS AS A LYMPHOKINE-ACTIVATED KILLER ATTRACTANT

Using an under agarose migration (UAM) assay, we studied lymphokine-ac tivated killer (LAK)-attractant activity in cultured conditioned mediu m of tumour tissues after chemotherapy as a possible mechanism of enha nced LAK cell accumulation into tumour tissues after chemotherapy. BMT -11 is a fibrosarcoma developed in C57BL/6 mice. The conditioned mediu m of BMT-11 tumour tissues obtained from mice treated with various ant i-cancer drugs had chemotactic activity for LAK cells (LAK-attractant activity). mRNA expression of interleukin (IL)-1 alpha, IL-6, IL-8, in terferon (IFN)-gamma, and tumour necrosis factor (TNF)-alpha was obser ved in untreated tumour tissues, which were not enhanced by cyclophosp hamide treatment. mRNA expression of TGF-beta 1 was not detected in un treated tumour tissues by reverse transcription-polymerase chain react ion (RT-PCR), but was detected in tumour tissues treated with cyclopho sphamide. Recombinant human TGF-beta 1 showed LAK-attractant activity at a concentration of 0.1 ng ml(-1) and 1 ng ml(-1), whereas fresh spl enocytes were not attracted by TGF-beta 1. Anti-TGF-beta 1 antibody in hibited LAK-attractant activity in the conditioned medium of tumour ti ssues treated with cyclophosphamide to approximately 35% that of contr ol at 100 mu g ml(-1). These findings indicate thar TGF-beta 1 produce d in the tumour tissues of mice treated with anticancer drugs could be a LAK attractant. By a 4 h Cr-51 release assay of natural killer cell -resistant BMT-11 tumour cells, we observed that TGF-beta 1 at a conce ntration from 0.01 ng ml(-1) to 10 ng ml(-1) did not inhibit LAR activ ity in an effector phase. Taken together, we suggest that TGF-beta 1 p roduced in tumour tissues after chemotherapy participates in gathering transferred LAK cells and contributes to the therapeutic effects of t ransferred LAK cells.