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Endogenous regulators of angiogenesis--emphasis on proteins with thrombospondin--type I motifs
1Department of Molecular, Cell and Developmental Biology, Molecular Biology Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA.
Abstract:
Angiogenesis has been acknowledged as an important requirement for growth and metastasis of tumors. Complete or partial suppression of vascular growth by a number of different strategies has been consistently associated with suppression of tumor expansion and even reduction of tumor burden. Consequently, identification of the molecular pathways of the angiogenic response has been a major focus of interest in academia and industry. The development of tumor-specific anti-angiogenic therapy was also catalyzed by the finding that inhibitors of angiogenesis appeared immune to the development of drug resistance by the tumor cells, a major restrain in current chemotherapy. Although the full identification of players and their cross-talk is still at its infancy, it appears that partial blockade of one of the steps in the angiogenesis cascade, is sufficient to affect capillary morphogenesis. Thus, suppression of specific integrin pathways or vascular endothelial growth factor signaling have been shown effective in the suppression of tumor-mediated angiogenesis and have led to subsequent initiation of clinical trials. In addition to the generation of antibodies or chemical mimetics to interfere with particular steps during vascular organization, several endogenous (or physiological) molecules have also been identified. The list of endogenous modulators of angiogenesis is growing and can offer additional and important tool for the generation of therapies to restrain tumor vascularization. This review will focus one group of such molecules which include the thrombospondins and metallospondins, two families of proteins linked by the presence of a conserved anti-angiogenic functional domain.
Insights
Tumor growth and metastasis depend on angiogenesis. Targeting molecular pathways with anti-angiogenic therapies, including endogenous proteins like thrombospondins, shows promise for cancer treatment by inhibiting tumor vascularization.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor growth and metastasis are critically dependent on angiogenesis, the formation of new blood vessels.
- Suppression of angiogenesis has been shown to inhibit tumor expansion and reduce tumor burden.
- Identifying molecular pathways of angiogenesis is crucial for developing effective cancer therapies.
Purpose of the Study:
- To review the molecular pathways involved in angiogenesis.
- To discuss the potential of anti-angiogenic therapies, including endogenous modulators, for cancer treatment.
- To focus on thrombospondins and metallospondins as key families of anti-angiogenic proteins.
Main Methods:
- Review of existing literature on angiogenesis and anti-angiogenic therapies.
- Analysis of molecular pathways, including integrin and vascular endothelial growth factor (VEGF) signaling.
- Identification and discussion of endogenous angiogenesis modulators.
Main Results:
- Partial blockade of angiogenesis pathways can effectively inhibit tumor vascularization.
- Inhibitors of angiogenesis appear to circumvent tumor drug resistance mechanisms.
- Thrombospondins and metallospondins possess conserved anti-angiogenic functional domains.
Conclusions:
- Targeting angiogenesis is a validated strategy for cancer therapy.
- Endogenous molecules like thrombospondins and metallospondins represent promising therapeutic targets.
- Further research into these protein families can lead to novel anti-angiogenic treatments.