Login

Journal Image
Current Pharmaceutical Biotechnology
ISSN (Print): 1389-2010
ISSN (Online): 1873-4316
VOLUME: 12
ISSUE: 12
DOI: 10.2174/138920111798808284      Price:  $58









The Complexities of TGF-β Action During Mammary and Squamous Cell Carcinogenesis

img
Author(s): Erin C. Connolly and Rosemary J. Akhurst
Pages 2138-2149 (12)
Abstract:
Many advanced tumors produce excess amounts of Transforming Growth Factor-β (TGF-β), which is a potent growth inhibitor of normal epithelial cells. However, in tumors its homeostatic action on cells can be diverted along several alternative pathways. Thus, TGF-β signaling has been reported to elicit a preventative or tumor suppressive effect during the earlier stages of tumorigenesis, but later in tumor development, when carcinoma cells become refractory to TGF-β-mediated growth inhibition, response to TGF-β signaling elicits predominantly tumor progressing effects. This is not a simple switch from suppression to progression, but more like a rheostat, involving multiple complementary and antagonizing activities that slowly tip the balance from one to the other. This review will focus on the multiple activities of TGF-β in regulation of two epithelial tumor types, namely squamous cell carcinoma and breast cancer. Basic findings in current mouse models of cancer are presented, as well as a discussion of the complicating issue of outcome of altered TGFβ signaling depending on genetic variability between mouse strains. This review also discusses the role TGF-β within the tumor microenvironment particularly its ability to polarize the microenvironment towards a pro-tumorigenic milieu.
Keywords:
TGF-β, tumor microenvironment, breast cancer, epithelial cells, pro-tumorigenic milieu, squamous cell carcinoma, epithelial, hematopoietic, immune cells, malignant carcinoma, epithelial to mesenchymal transformation (EMT), multi-stage tumorigenesis model, lymph nodes and lungs, immature state, bone metastasis
Affiliation:
UCSF Helen Diller Family Cancer Research Building, San Francisco, CA 94158-9001, USA.