The Anti-Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) D16F7 Monoclonal Antibody Inhibits Melanoma Adhesion to Soluble VEGFR-1 and Tissue Invasion in Response to Placenta Growth Factor

Abstract

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family involved in tumor-associated angiogenesis and melanoma invasion of the extra-cellular matrix (ECM) through activation of membrane VEGF receptor 1 (VEGFR-1). A soluble VEGFR-1 (sVEGFR-1) form is released in the ECM, where it sequesters proangiogenic factors and stimulates endothelial or tumor cell adhesion and chemotaxis through interaction with α5β1 integrin. The anti-VEGFR-1 monoclonal antibody (D16F7 mAb) inhibits VEGF-A or PlGF-mediated signal transduction without affecting ligand interaction, thus preserving sVEGFR-1 decoy function. The aim of this study was to investigate whether D16F7 mAb hampers melanoma spread by in vitro analysis of cell adhesion to sVEGFR-1, ECM invasion, transmigration through an endothelial cell monolayer and in vivo evaluation of tumor infiltrative potential in a syngeneic murine model. Results indicate that D16F7 mAb significantly inhibits melanoma adhesion to sVEGFR-1 and ECM invasion, as well as transmigration in response to PlGF. Moreover, treatment of melanoma-bearing mice with the anti-VEGFR-1 mAb not only inhibits tumor growth but also induces a significant reduction in bone infiltration associated with a decrease in PlGF-positive melanoma cells. Furthermore, D16F7 mAb reduces PlGF production by melanoma cells. Therefore, blockade of PLGF/VEGFR-1 signaling represents a suitable strategy to counteract the metastatic potential of melanoma.

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum—Does the Common Pathophysiological Pathway Exist?

“…The above circumstances occur in high levels of PlGF concentration in cancer tissues, which contribute to their proliferation, progression, local invasion, lymph, and distant metastases through blood flow, poor response to treatment, and implicate poor survival [14]. This occurs in various types of cancers, such as melanoma, small-cell lung cancer, thyroid carcinoma, serous ovarian cancer (OC), and oral squamous cell carcinoma [14,[19][20][21][22][23][24][25].…”

Angiogenesis Still Plays a Crucial Role in Human Melanoma Progression

“…Additionally, D16F7 mAb reduces PlGF production by melanoma cells. In conclusion, this study suggested that blocking PlGF/VEGFR-1 signaling with D16F7 mAb represents a promising strategy to counteract the metastatic potential of melanoma by inhibiting tumor-associated angiogenesis and invasion [35].…”

“…VEGF-C and VEGF-D act as lymphangiogenic growth factors signaling via VEGFR-2 and VEGFR-3, and the lack of the VEGF-C in mice results in compromised development of the lymphatic vasculature [34,35]. VEGF-C is expressed in primary and metastatic melanoma and is associated with high intratumoral lymphatic density [36][37][38].…”

Programmed Cell Death Pathways in Cholangiocarcinoma: Opportunities for Targeted Therapy

“…Numerous studies highlight the implication of microRNAs (miRNAs) in cancer research, as they play an important role in regulating cancer cells and impacting various aspects of cancer progression, including apoptosis induction, cell cycle regulation, metastasis promotion, and angiogenesis stimulation [30,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. In a recent investigation by Xiong et al [79], the effects of circSETD3, a circular RNA containing multiple miRNA binding sites, were studied in CCA cells.…”