Related Experiment Videos
Transforming growth factor-beta system and its regulation by members of the steroid-thyroid hormone superfamily
1Department of Virology, Haartman Institute, Helsinki, Finland.
Abstract:
TGF-beta s and their receptors are expressed ubiquitously, and they act as key regulators of many aspects of cell growth, differentiation, and function. Steroid action on target tissues is often associated with increase in TGF-beta isoforms. Regulation of TGF-beta expression and activation is crucial for normal development and growth control. The loss of responsiveness of different tumor cells to the antiproliferative effects of TGF-beta is a common feature in carcinogenesis. Multiple changes are required for the cells to gain complete resistance to TGF-beta growth inhibition (Fynan and Reiss, 1993; Kimchi et al., 1988; Samuel et al., 1992). Although many tumor cells are not growth inhibited by TGF-beta, they respond to TGF-beta treatment by changes in the expression of matrix components and enhanced proteolytic activity (KeskiOja et al., 1988). Agents that induce TGF-beta production in target tissues can have a chemopreventive or chemotherapeutic value for the management of epithelial malignancies. Conversely, data supporting a positive role for TGF-beta in established tumor progression are beginning to emerge (Arteaga et al., 1993a,b; Barrett-Lee et al., 1990; Arrick et al., 1992 ; E. A. Thompson et al., 1991). In later stages of tumor development, cell proliferation is often not inhibited by TGF-beta, and tumor cells secrete large amounts of this growth factor (Fynan and Reiss, 1993). In vivo TGF-beta secreted by tumor or stromal cells can influence host responses such as a natural killer cell function and thus indirctly support tumor cell viability (Arteaga et al., 1993b). TGF-beta may also affect tumor growth indirectly by stromal effects and promotion of angiogenesis. TGF-beta may also be involved in the progression of breast tumors from the steroid-sensitive to steroid-insensitive state (King et al., 1989). Understanding of the net effect of TGF-beta in different stages of tumor development is critical for the evaluation of its therapeutic value in cancer treatment.
Insights
Transforming growth factor-beta (TGF-β) regulates cell functions, but tumor cells often lose sensitivity to its growth inhibition. Understanding TGF-β
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Transforming growth factor-beta (TGF-β) and its receptors are widely expressed, regulating cell growth, differentiation, and function.
- TGF-β signaling is crucial for normal development, but resistance to its antiproliferative effects is a hallmark of carcinogenesis.
- Tumor cells often lose TGF-β growth inhibition but respond with altered matrix production and proteolytic activity.
Purpose of the Study:
- To explore the multifaceted role of TGF-β in various stages of tumor development.
- To evaluate the potential of TGF-β inducers for cancer chemoprevention and chemotherapy.
- To understand the complex effects of TGF-β on tumor progression and host responses.
Main Methods:
- Review of existing literature on TGF-β signaling in normal development and cancer.
- Analysis of studies investigating TGF-β's impact on tumor cell proliferation and extracellular matrix.
- Examination of TGF-β's role in tumor progression, angiogenesis, and immune modulation.
Main Results:
- Loss of TGF-β responsiveness is common in tumor cells, requiring multiple genetic changes.
- Tumor cells can exhibit altered responses to TGF-β, including matrix remodeling and enhanced proteolysis.
- TGF-β can promote tumor progression indirectly via stromal effects, angiogenesis, and immune suppression.
Conclusions:
- Agents inducing TGF-β may hold chemopreventive or chemotherapeutic potential for epithelial malignancies.
- TGF-β plays a dual role, potentially inhibiting early growth but promoting later-stage tumor progression.
- Understanding TGF-β's net effect across tumor development stages is critical for its therapeutic application in cancer.