Acidic cellular environments: activation of latent TGF-beta and sensitization of cellular responses to TGF-beta and EGF.
Int J Cancer
; 43(5): 886-91, 1989 May 15.
Article
in En
| MEDLINE
| ID: mdl-2785508
ABSTRACT
Transient (about 2 hr) acidification to approx. pH 5.0 of agar-gelled overlayers containing untransformed NRK-49F or KiMSV-transformed NRK-49F cells in the presence of fetal calf serum or crude 49F-cell conditioned medium, as sources of latent TGF-beta, elicited EGF-dependent colony formation of 49F cells and inhibited spontaneous growth of transformed cells. Pure, active TGF-beta (porcine, type I) had the same effects on these respective cell types, suggesting that the above results were due to activation of latent TGF-beta in the transiently acidic cellular environment. Similar acidifications in the absence of a source of latent TGF-beta enhanced the positive growth response of 49F and AKR-2B cells to EGF and active TGF-beta and also the negative growth response of KiMSV-transformed 49F cells to active TGF-beta. These results are compatible with the idea that acidic cellular environments, particularly in tumor tissues, are conducive to activation of latent TGF-beta, perhaps in conjunction with other activating mechanisms, and to an enhanced response to some growth factors. However, the heterogeneity of cell populations within tumoral masses presents an obstacle to a clear understanding of the consequences of such activation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factors
/
Cell Transformation, Neoplastic
/
Epidermal Growth Factor
Limits:
Animals
Language:
En
Journal:
Int J Cancer
Year:
1989
Document type:
Article
Affiliation country:
France