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Particular Types of Tumor Cells Have the Capacity to Convert Transforming Growth Factor ß from a Latent to an Active Form¹

Biomedical Research Center, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka 565 [H. T., T. T., X-F. L., M. O., H. F., T. H.]; Research Laboratories, King Brewing Co., Ltd., Kakogawa 675-01 [T. I.]; and Department of Immunology, Kochi Medical College, Nangoku 783 [S. F.], Japan

We investigated the capacities of various tumor types to generate an active versus latent form of transforming growth factor ß (TGF-ß) in its culture supernatants (SNs). Tumor cell lines were divided into three types depending on the form and magnitude of TGF-ß detected in their culture SNs: some (2 of 7 lines) generated mostly an active form (Type A); others (4 of 7) generated exclusively a latent form (Type B); and the remaining line (1 of 7) produced only marginal levels of active/latent TGF-ß (Type C). When Type A tumor cells were cultured at lower numbers, cultures failed to generate active TGF-ß. However, the addition of Type B tumor cell culture SNs containing only a latent form of TGF-ß resulted in the generation of the potent activity of active TGF-ß. This capacity was observed for another Type A tumor but not for other types (Type B and Type C). An active form of TGF-ß was detected in culture SNs of Type A tumor cells as early as 3–6 h after the addition of Type B tumor culture SNs. The emergence of an active form of TGF-ß was also observed in cultures of Type A tumor cells, the protein synthesis of which was almost completely inhibited by pretreatment with cycloheximide. Moreover, the Type B tumor SN used for the induction of active TGF-ß activity was found to contain latent TGF-ß with an apparent molecular weight of about 200,000. Type A tumor cells were also capable of generating active TGF-ß by the addition of recombinant TGF-ß of latent form with a small molecular weight (about 60,000), although the generation of active TGF-ß was much weaker after the addition of small latent TGF-ß than after the addition of large latent TGF-ß. Taken collectively, these results indicate that particular types of tumor cells have the capacity to generate an active form of TGF-ß and that such capacity can be attributed to their potential to convert TGF-ß from a latent (mainly large type) to an active form.

¹ Supported by Special Project Research-Cancer Bioscience from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 4/ 3/92. Accepted 8/ 4/92.

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