Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB.

Abstract

Human WM9 melanoma cells, previously shown to be devoid of PDGF expression, were stably transfected with a PDGF-B cDNA under the transcriptional control ofa cytomegalovirus promoter. Northern blot analysis revealed

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cancers, in 52% of ovarian cancers, in 65% of breast cancers, and in 51% of lung cancers (N. Loizos, ImClone Systems, unpublished results).…”

“…59 Investigations in multiple cancer types have highlighted the relevance of both PDGF-activated tumor and supporting stromal cells in facilitating cancer growth and metastasis. [44][45][46][47][48][49][50][51]55,57,60 In some cases, specific autocrine or paracrine mechanisms that contribute to malignant progression have been suggested. In 1 experiment, NIH 3T3 cells were transformed when PDGF-A or PDGF-B gene expression was induced using a transfected promoter.…”

“…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.…”

Collagen type I expression in experimental anaplastic thyroid carcinoma: Regulation and relevance for tumorigenicity

“…8,[12][13][14][15] The mechanisms by which carcinoma cells stimulate stromal connective tissue cells are poorly understood, although data suggesting that transfer of stimulatory factors occurs by a paracrine mechanism have been presented. 14,16 Platelet-derived growth factor (PDGF) induces a stromal response in tumors 17 and induces translation of procollagen type I mRNAs in fibroblasts in which cell spreading has been impaired. 18 Transforming growth factor-␤ (TGF-␤) activates the type I collagen genes, as well as collagen production in vitro and in vivo, 19,20 and has been ascribed to be involved in the formation of tumor desmoplasia, e.g., in scirrhous gastric cancer.…”

Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization

“…In mice, implantation of PDGF B-chain-transfected melanoma cells resulted in increased fibrovascular stroma development relative to untransfected cells. 14 Administration of PDGF B-chain to the chick chorioallantoic membrane resulted in increased numbers of vessels with little inflammation. 15,16 In vitro studies similarly suggested that PDGF B-chain could be proangiogenic under some conditions, and that its target could be either ECs, or vascular smooth muscle cells (SMCs), or both.…”