Drug Target for Cancer: PDGFR-β

Drug Targets for Cancer: PDGFR-β and Cancer

PDGFR-β is usually undetectable in quiescent endothelial cells (ECs), but it is expressed by ECs of several human tumors, and capillaries are frequently surrounded by PDGFR-β-positive perivascular cells. Whereas PDGFR-β expression is common on tumor-associated pericytes, its expression on tumor-associated ECs appears to be more restricted. Overexpression of PDGFR-β has been demonstrated by in situ hybridization in the proliferative endothelium of gliomas. In experimental mouse models it was shown that PDGFR-inhibitor imatinib associated to chemotherapy enhanced the therapeutic response, and tumor regression was associated with increased ECs apoptosis. PDGFR-β is expressed by both breast cancer cells and tumor-associated ECs in 69.7% of the cases. It was shown that breast cancer cells induce PDGFR-β, but not PDGFRα expression in the adjacent ECs. The angiogenic effect of PDGFR-β was demonstrated by increased value of microvascular density (MVD), compared with PDGFR-β-negative specimens. Additionally, PDGFR-β was found in ECs growing in a bone metastasis breast cancer model. In human specimens of breast cancer, both PDGFRα and β are expressed in the blood vessel wall. A differential expression was found in the stromal cells. PDGFR-β is expressed in a significant higher number of tumor-associated stromal cells than PDGFRα. PDGFR are also expressed by tumor cells, but the pattern of the positive reaction is again, different. PDGFRα is expressed in less than one third of the cases with moderate intensity and heterogeneous distribution. PDGFR-β expression in tumor cells was found in more than two thirds of the cases, with strong and homogeneous distribution. The most important aspect that comes from microscopic data is the increased expression of PDGFR in invasive breast cancer in neoplastic cells, stromal cells and blood vessels, as compared with the normal tissue and premalignant conditions. These data indirectly support the link between tumor progression and angiogenesis induced by the PDGF signaling. Similar data were found in patients with prostate cancer, where PDGFR expression was associated with tumor progression and overexpression was found in the majority of bone metastasis. Taken together, these findings support the introduction of anti- PDGFR-β antiangiogenic therapy in cancers with PDGFR-β-positive ECs.

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Drug Targets for Cancer: PDGFR-β Related Reference

Raica M, Cimpean A M. Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy[J]. Pharmaceuticals, 2010, 3(3): 572-599.

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