Particular types of tumor cells have the capacity to convert transforming growth factor beta from a latent to an active form.
We investigated the capacities of various tumor types to generate an active versus latent form of transforming growth factor beta (TGF-beta) in its culture supernatants (SNs). Tumor cell lines were divided into three types depending on the form and magnitude of TGF-beta 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-beta (Type C). When Type A tumor cells were cultured at lower numbers, cultures failed to generate active TGF-beta. However, the addition of Type B tumor cell culture SNs containing only a latent form of TGF-beta resulted in the generation of the potent activity of active TGF-beta. This capacity was observed for another Type A tumor but not for other types (Type B and Type C). An active form of TGF-beta 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-beta 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-beta activity was found to contain latent TGF-beta with an apparent molecular weight of about 200,000. Type A tumor cells were also capable of generating active TGF-beta by the addition of recombinant TGF-beta of latent form with a small molecular weight (about 60,000), although the generation of active TGF-beta was much weaker after the addition of small latent TGF-beta than after the addition of large latent TGF-beta. Taken collectively, these results indicate that particular types of tumor cells have the capacity to generate an active form of TGF-beta and that such capacity can be attributed to their potential to convert TGF-beta from a latent (mainly large type) to an active form.
Takiuchi
H
H
Biomedical Research Center, Osaka University Medical School, Japan.
Tada
T
T
Li
X F
XF
Ogata
M
M
Ikeda
T
T
Fujimoto
S
S
Fujiwara
H
H
Hamaoka
T
T
D000818:Animals; D002474:Cell-Free System; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D005354:Fibrosarcoma / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D001357:Sarcoma, Avian / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000145:classification / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D016212:Transforming Growth Factor beta; D003513:Cycloheximide