Placental Growth Factor and Vascular Endothelial Growth Factor Together Regulate Tumour Progression via Increased Vasculature in Cutaneous T-cell Lymphoma

Abstract

Angiogenesis is regarded as an essential step in supporting tumour growth and metastasis. In haematological malignancies, including cutaneous T-cell lymphoma (CTCL), angiogenesis is increased and serum levels of some pro-angiogenic markers are elevated. The aim of this study was to investigate expression levels of placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)-A in lesional skin and sera in patients with CTCL, and to assess the association of these factors with development of CTCL. A further aim was to investigate the effect of PlGF on lymphoma cell growth in vivo using a tumour inoculation model. Expression of PlGF and VEGF-A were significantly elevated in CTCL skin. Tumour cells expressed PlGF in some cases. Serum PlGF levels were increased in patients with advanced CTCL and correlated with disease markers. Moreover, PlGF enhanced lymphoma cell growth in vivo through increasing tumour vasculature. These findings suggest that angiogenesis plays a role in the progression of CTCL and raises the possibility of using inhibitors of PlGF in CTCL therapy.

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

“…In line with the growing microvessel density, a variety of angiogenic factors are increased in the lesional skin of CTCL patients when compared with normal skin or skin from patients with benign inflammatory skin conditions (Krejsgaard et al, 2006;Miyagaki et al, 2012aMiyagaki et al, , 2017Kawaguchi et al, 2014;Lauenborg et al, 2015;Sakamoto et al, 2018;Suzuki et al, 2020). Although some of these are expressed by stromal cells, the majority mainly appear to be produced by the malignant T cells.…”

“…Although some of these are expressed by stromal cells, the majority mainly appear to be produced by the malignant T cells. For instance, atypical T cells in CTCL lesions stain positive for the highly angiogenic protein VEGF-A, and malignant CTCL cell lines produce VEGF-A via a JAK-and c-Jun N-terminal kinase (JNK)-dependent mechanism in vitro (Krejsgaard et al, 2006;Miyagaki et al, 2017;Sakamoto et al, 2018). Besides being a potent stimulator of angiogenesis, VEGF-A also has the capacity to enhance the expression of TSLP in keratinocytes and, accordingly, the serum concentrations of VEGF-A correlate with the lesional expression of TSLP in erythrodermic CTCL patients (Sakamoto et al, 2018).…”

Serum vascular endothelial growth factor A levels reflect itch severity in mycosis fungoides and Sézary syndrome

“…VEGF‐A activates VEGF receptor (VEGFR)‐1 and VEGFR‐2 on vascular endothelial cells. VEGF‐A is secreted by tumor cells of MF/SS and its expression in lesional skin correlated with CCL27 expression, a potential disease marker . On the other hand, VEGFR‐1 and VEGFR‐2 are not expressed on tumor cells .…”

Curcumin analog, GO‐Y078, overcomes resistance to tumor angiogenesis inhibitors

“…We also examined the inhibition of tumor angiogenesis with GO‐Y078 in nude mice inoculated with CTCL cell line HH. VEGF regulates tumor angiogenesis of CTCL . Use of GO‐Y078 ointment could significantly inhibit the angiogenesis surrounding the skin tumors as well as skin tumor apoptosis (Figure ).…”