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The angiogenic asset of soft tissue sarcomas: a new tool to discover new therapeutic targets.

Rocchi L, Caraffi S, Perris R, Mangieri D - Biosci. Rep. (2014)

Bottom Line: Nevertheless, this does not exclude the possibility that angiogenesis could be important in STS.The importance of neoangiogenesis in soft tissue tumours is confirmed by the arising number of publications comparing angiogenesis mediators with clinical features of patients with STS.The efficacy of anti-angiogenic therapies in other types of cancer is well documented.

View Article: PubMed Central - PubMed

Affiliation: *Unità Operativa di Anatomia e Istologia Patologica, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci, 14, 43100-Parma, Italy.

ABSTRACT
STS (soft tissue sarcomas) are rare malignant tumours deriving from cells of mesenchymal origin and represent only 1% of all malignant neoplasms. It has been extensively demonstrated that angiogenesis has an important role in cancer malignancy. Particularly, a lot of studies demonstrate the importance of angiogenesis in the development of carcinomas, whereas little is known about the role of angiogenesis in sarcomas and especially in STS. This review aims at summarizing the new discoveries about the nature and the importance of angiogenesis in STS and the new possible therapeutic strategies involved. Only a few studies concerning STS focus on tumour neovascularization and proangiogenic factors and look for a correlation with the patients prognosis/survival. These studies demonstrate that intratumoural MVD (microvessels density) may not accurately represent the angiogenic capacity of STS. Nevertheless, this does not exclude the possibility that angiogenesis could be important in STS. The importance of neoangiogenesis in soft tissue tumours is confirmed by the arising number of publications comparing angiogenesis mediators with clinical features of patients with STS. The efficacy of anti-angiogenic therapies in other types of cancer is well documented. The understanding of the involvement of the angiogenic process in STS, together with the necessity to improve the therapy for this often mortal condition, prompted the exploration of anti-tumour compounds targeting this pathway. In conclusion, this review emphasizes the importance to better understand the mechanisms of angiogenesis in STS in order to subsequently design-specific target therapies for this group of poorly responding tumours.

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Related in: MedlinePlus

New angiogenic targets in STSNew possible angiogenic targets in STS are represented. The yellow boxes indicate the targets for new drug development for STS. TIMP2- synthetic peptides could block or retard extra-cellular matrix degradation, a crucial step in tumour cells migration. Monoclonal antibodies against FGF2 and CSF-1 could interfere with the endothelial cells activation and the consequent new-angiogenesis, a crucial step for tumour mass survival and metastatization. The use of small molecule directed to the FGF2-receptor could have an analogue effect. PIGF analogues could normalize the tumour vessel blocking tumour cells extravasation.
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Figure 1: New angiogenic targets in STSNew possible angiogenic targets in STS are represented. The yellow boxes indicate the targets for new drug development for STS. TIMP2- synthetic peptides could block or retard extra-cellular matrix degradation, a crucial step in tumour cells migration. Monoclonal antibodies against FGF2 and CSF-1 could interfere with the endothelial cells activation and the consequent new-angiogenesis, a crucial step for tumour mass survival and metastatization. The use of small molecule directed to the FGF2-receptor could have an analogue effect. PIGF analogues could normalize the tumour vessel blocking tumour cells extravasation.

Mentions: When considering novel therapeutic targets, some other proteins need to be mentioned. In non-gynecological leiomyosarcoma, macrophage CSF1 (colony-stimulating factor 1) showed a stronger correlation with tumour vascularization than VEGF, resulting in a possible candidate for target therapy [121]. In a murine model of fibrosarcoma, PlGF (placental growth factor), a ligand of VEGFR-1, showed important effects on vascular remodelling and normalization, altering tumour growth. Thus, modulation of PlGF concentration or PlGF analogue synthesis could be used as a new therapeutic approach [58]. A representation of possible new targets is schematized in Figure 1.


The angiogenic asset of soft tissue sarcomas: a new tool to discover new therapeutic targets.

Rocchi L, Caraffi S, Perris R, Mangieri D - Biosci. Rep. (2014)

New angiogenic targets in STSNew possible angiogenic targets in STS are represented. The yellow boxes indicate the targets for new drug development for STS. TIMP2- synthetic peptides could block or retard extra-cellular matrix degradation, a crucial step in tumour cells migration. Monoclonal antibodies against FGF2 and CSF-1 could interfere with the endothelial cells activation and the consequent new-angiogenesis, a crucial step for tumour mass survival and metastatization. The use of small molecule directed to the FGF2-receptor could have an analogue effect. PIGF analogues could normalize the tumour vessel blocking tumour cells extravasation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219423&req=5

Figure 1: New angiogenic targets in STSNew possible angiogenic targets in STS are represented. The yellow boxes indicate the targets for new drug development for STS. TIMP2- synthetic peptides could block or retard extra-cellular matrix degradation, a crucial step in tumour cells migration. Monoclonal antibodies against FGF2 and CSF-1 could interfere with the endothelial cells activation and the consequent new-angiogenesis, a crucial step for tumour mass survival and metastatization. The use of small molecule directed to the FGF2-receptor could have an analogue effect. PIGF analogues could normalize the tumour vessel blocking tumour cells extravasation.
Mentions: When considering novel therapeutic targets, some other proteins need to be mentioned. In non-gynecological leiomyosarcoma, macrophage CSF1 (colony-stimulating factor 1) showed a stronger correlation with tumour vascularization than VEGF, resulting in a possible candidate for target therapy [121]. In a murine model of fibrosarcoma, PlGF (placental growth factor), a ligand of VEGFR-1, showed important effects on vascular remodelling and normalization, altering tumour growth. Thus, modulation of PlGF concentration or PlGF analogue synthesis could be used as a new therapeutic approach [58]. A representation of possible new targets is schematized in Figure 1.

Bottom Line: Nevertheless, this does not exclude the possibility that angiogenesis could be important in STS.The importance of neoangiogenesis in soft tissue tumours is confirmed by the arising number of publications comparing angiogenesis mediators with clinical features of patients with STS.The efficacy of anti-angiogenic therapies in other types of cancer is well documented.

View Article: PubMed Central - PubMed

Affiliation: *Unità Operativa di Anatomia e Istologia Patologica, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci, 14, 43100-Parma, Italy.

ABSTRACT
STS (soft tissue sarcomas) are rare malignant tumours deriving from cells of mesenchymal origin and represent only 1% of all malignant neoplasms. It has been extensively demonstrated that angiogenesis has an important role in cancer malignancy. Particularly, a lot of studies demonstrate the importance of angiogenesis in the development of carcinomas, whereas little is known about the role of angiogenesis in sarcomas and especially in STS. This review aims at summarizing the new discoveries about the nature and the importance of angiogenesis in STS and the new possible therapeutic strategies involved. Only a few studies concerning STS focus on tumour neovascularization and proangiogenic factors and look for a correlation with the patients prognosis/survival. These studies demonstrate that intratumoural MVD (microvessels density) may not accurately represent the angiogenic capacity of STS. Nevertheless, this does not exclude the possibility that angiogenesis could be important in STS. The importance of neoangiogenesis in soft tissue tumours is confirmed by the arising number of publications comparing angiogenesis mediators with clinical features of patients with STS. The efficacy of anti-angiogenic therapies in other types of cancer is well documented. The understanding of the involvement of the angiogenic process in STS, together with the necessity to improve the therapy for this often mortal condition, prompted the exploration of anti-tumour compounds targeting this pathway. In conclusion, this review emphasizes the importance to better understand the mechanisms of angiogenesis in STS in order to subsequently design-specific target therapies for this group of poorly responding tumours.

Show MeSH
Related in: MedlinePlus