PDGF BB induces VEGF secretion in ovarian cancer

Abstract

We identified the platelet derived growth factor receptor (PDGFR)

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

“…These signaling ways induces angiogenesis by increasing sprouting, vessel dilation, and the detachment of pericytes from pre-existing vessels, and the subsequent increase in blood supply potently facilitates rapid tumor growth and metastasis 40,41 . These findings make the angiogenic growth factor system an attractive oncologic therapeutic target 42 . In addition, experimental data from several clinical trials suggest the possible benefits of anti-platelet drugs in limiting tumor initiation and progression.…”

“…In addition, experimental data from several clinical trials suggest the possible benefits of anti-platelet drugs in limiting tumor initiation and progression. Many novel VEGF/VEGFR-targeted inhibitors have been reported to improve the prognosis and survival of patients more than chemotherapy alone does 42 , such as bevacizumab and ramucirumab [43][44][45] . However, when VEGF signaling is blocked, other compensatory angiogenic signaling pathways can regulate tumor angiogenesis, including the PDGF, FGF, and hepatocyte growth factor/Met signaling pathways 46 .…”

Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α

“…2). [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] Several types of cancers, particularly those derived from the ovary, prostate, breast, lung, brain, skin, and bone, express PDGFRa on the malignant cells themselves (Table 1). 22 In 1 experiment in which a human tumor array was probed with a cross-reactive polyclonal rabbit antibody to PDGFRa, PDGFRa expression was noted in approximately 95% of osteosarcomas and chondrosarcomas, in 77% of prostate cancers, in 52% of ovarian cancers, in 65% of breast cancers, and in 51% of lung cancers (N. Loizos, ImClone Systems, unpublished results).…”

“…PDGFs can influence cancer growth and malignant angiogenesis through several mechanisms, including the activation of PDGFRa expressed on cancer cells, stromal fibroblasts, and vascular endothelial cells and by PDGF-induced production of vascular endothelial growth factor (VEGF) by stromal cells. [45][46][47][48][49][50][51][52][53][54][55]57,60 The asterisk indicates that Table 1 required for the development of malignant stroma, 46 a separate study indicated that the induction of PDGF-CC expression in melanoma cells led to accelerated tumor growth through the activation of PDGFRa. 47 In the latter study, the exclusive expression of PDGFRa on cancerassociated stromal fibroblasts illuminated a paracrine mechanism of stromal-regulated melanoma tumor growth.…”

“…45,57 It also has been established that an intact PDGF/ PDGFRa axis is required for vascular endothelial growth factor (VEGF) production by tumor stroma and for the regulation of malignant angiogenesis in tumors that are resistant to antiangiogenic treatment. [52][53][54] The former was demonstrated in an elegant experiment in which VEGF-null fibrosarcomas grown in mice required the recruitment of PDGFRa-expressing stromal fibroblasts for VEGF production, angiogenesis, and tumorigenesis. 52 The recruitment of PDGFRa-expressing stromal fibroblasts depended on paracrine stimulation by PDGF-AA produced from the tumor cells.…”