Expression Patterns of Placenta Growth Factor in Human Melanocytic Cell Lines

Abstract

Expression patterns of the angiogenic placenta growth factor and its receptor neuropilin-1 were assessed in normal human melanocytes, SV40T-transformed melanocytes, and melanoma cells derived from primary and metastatic lesions. As determined by reverse transcription-polymerase chain reaction all primary and metastatic melanoma cell lines tested and SV40T-transformed melanocytes coexpressed two placenta growth factor splice variants (placenta growth factor-1 and -2) as well as neuropilin-1 mRNA. Placenta growth factor protein was detected in conditioned media derived from five of eight melanomas and from SV40T-transformed melanocytes. In contrast to melanoma cells, normal melanocytes did not express placenta growth factor mRNA at detectable levels and did not secrete placenta growth factor protein. By contrast, neuropilin-1 transcripts were detected in some of the normal melanocytes. Secretion of placenta growth factor by melanoma cells appeared to be constitutive because it was not affected by the addition of exogenous growth factors including insulin, epidermal growth factor, or basic fibroblast growth factor to culture media. Although melanoma cells expressed both, neuropilin-1 and flt-1, exogenous homodimeric placenta growth factor had no effect on melanoma cell growth. Similarly, placenta growth factor did not induce urokinase-type plasminogen activator production in these cells. These findings demonstrate that melanoma progression is accompanied by deregulated, constitutive placenta growth factor expression. Placenta growth factor, however, serves no apparent autocrine role in melanoma proliferation. Further studies are needed to define the relative contribution of placenta growth factor to the angiogenic properties of human melanomas.

A comprehensive study of iRGD-modified liposomes with improved chemotherapeutic efficacy on B16 melanoma

“…The different expression levels could be compared by the number of positive cells and were in accordance with previous reports (Kramer et al, 1991;Graeven et al, 2000;Pellet-Many et al, 2008;Yang et al, 2010). Previous researches showed the modifying density could affect the targeting efficiency of peptide ligand (Gu et al, 2008;Waite & Roth, 2011).…”

Angiogenesis, lymphangiogenesis, and melanoma metastasis

“…Although overexpression of bFGF conferred the capacity for anchorage-independent growth to human and murine melanocytes in vitro, bFGF-transfected melanocytes did not form persisting malignant tumors in vivo, indicating that autocrine bFGF stimulation provides a growth advantage but is not sufficient for the induction of a transformed phenotype (Dotto et al, 1989;Nesbit et al, 1999;Graeven et al, 2001). Interference with the bFGF pathway in melanoma cells by antisense approaches and overexpression of a dominant-negative mutant FGF receptor 1 was shown to inhibit in vitro cell proliferation and in vivo tumorigenesis (Becker et al, 1989(Becker et al, , 1992Yayon et al, 1997), whereas overexpression of bFGF promoted the in vivo tumor growth and tumor angiogenesis of WM164 melanoma cells (Graeven et al, 2001). In these studies, downregulation of VEGF expression slowed tumor growth, whereas transfection of a bFGF antisense construct completely inhibited tumor formation, indicating an important autocrine function of bFGF in human melanoma development.…”

Placental Growth Factor Upregulation Is a Host Response to Antiangiogenic Therapy

“…PlGF transcripts were present in human cervical squamous cell carcinomas and were upregulated in human prostate cancer cells (15,16). Human melanoma cells and melanocytes also secrete and respond to PlGF (17,18). In addition, PlGF is of interest as a target for breast and gastric cancers in which the expression is higher than in other cancers (19,20).…”

“…sFLT01 functions as a soluble VEGFR-1 decoy receptor and neutralizes mouse VEGF-A and PlGF (mVEGF-A, mPlGF) and human VEGF-A and PlGF (hVEGF-A, hPlGF). The B16F10 melanoma model was selected on the basis of reports that human melanoma cells secrete hPlGF and also because the B16F10 model has been utilized to evaluate antibodies against PlGF in earlier reports (8,17,18,22,31). The A673 Ewing's sarcoma xenograft model was employed since previous studies investigated antiangiogenic agents that target VEGF-A in this model and/or the contribution of host stroma to mVEGF production (36,37).…”