Overexpression of both platelet-derived growth factor-BB and vascular endothelial growth factor-C and its association with lymphangiogenesis in primary human non-small cell lung cancer

Abstract

BackgroundMetastatic spread of tumor through lymphatic vasculature is an important adverse prognostic factor in a variety of human cancer and tumor lymphangiogenesis requires the interplay of several growth factors. Platelet-derived growth factor (PDGF)-BB and vascular endothelial growth factor (VEGF)-C are two important molecules involving in tumor metastasis and lymphangiogenesis. Therefore, the aim of this study was to investigate the coexpression of PDGF-BB and VEGF-C in primary human non-small cell lung cancer (NSCLC) and its association with lymphangiogenesis.MethodsUsing immunohistochemical staining, PDGF-BB and VEGF-C expression were detected in 109 primary NSCLC tissues, while the lymphatic micro-vessel density (LMVD) was counted.ResultsOf 109 cases, PDGF-BB and VEGF-C overexpression was 66.97% (73/109) and 65.14% (71/109), respectively. 52 (47.7%) had overexpression of both PDGF-BB and VEGF-C (P + V+), 21 (19.3%) overexpression of PDGF-BB but low expression of VEGF-C (P + V-), 19(17.4%) overexpression of VEGF-C but low expression of PDGF-BB (P-V+) and 17(15.6%) low expression of both PDGF-BB and VEGF-C (P-V-). PDGF-BB expression was positively related to that of VEGF-C (r = 0.451, p = 0.034). LMVD in cases with P + V + was much higher than those with P-V- (p = 0.004). In addition, the patients with P + V + were younger and also had larger tumor size, more likely lymph node metastasis and worse histological differentiation than those with P-V-. Moreover, the overall survival (OS) of patients with P + V + was shorter than those with P-V- (p = 0.015).ConclusionCoexpression of both PDGF-BB and VEGF-C was associated with lymphangiogenesis and poor prognosis in NSCLC, and might play a critical role in NSCLC progression.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2261801312571320

Nuclear factor of activated T cells in cancer development and treatment

“…VEGFC and platelet-derived growth factor BB (PDGF-BB) have been extensively studied in lymphangiogenesis [94,95]. VEGFC and PDGF-BB co-expression is also related to lymphangiogenesis in lung cancer [96]. The results above suggest that both the VEGFC/NFAT1 and PDGF/ NFAT1 pathways are involved in tumor lymphangiogenesis.…”

Platelet-Derived Growth Factor Signaling in the Lung. From Lung Development and Disease to Clinical Studies

“…The expression of PDGFRa/b and PDGF-A/B in NSCLC is associated with poor prognosis (170)(171)(172). PDGF signaling is important for tumor growth, angiogenesis, and lymphangiogenesis in vivo; this was affected by coexpression of PDGF-BB and VEGF-C (or VEGFR3) in NSCLC, also resulting in poor prognosis (172)(173)(174). The angiogenic properties of PDGF ligands are supported by the finding that PDGF-AA regulates VEGF expression in an autocrine way and facilitates the malignant process of transforming precancerous lesions to advanced cancer (175).…”

Platelet‐derived growth factor (PDGF) signalling in cancer: rapidly emerging signalling landscape

“…Non‐small cell lung cancer (NSCLC) patients who had overexpression of both PDGF‐BB and VEGF‐C presented with higher tumour growth and lymphatic invasion . Crenolanib has been shown to be effective against PDGFR and induced apoptosis in NSCLC A549 cells.…”

“…However, T β RII endocytosis and SMAD2 phosphorylation were not noted in PDGFR α ‐silenced cells. Human colorectal cancer HT29 cells were implanted into the liver of severe combined immunodeficiency mice, and results revealed that HT29 cells colonization in the liver induced activation of HSCs as evidenced by upregulated expression of PDGFR α in HSCs …”