PF4V1 affects the progression of oral squamous cell carcinoma by regulating Wnt/\u03b2-catenin pathway and angiogenesis

Cuiping Li,Weidong Jiang,Xuanping Huang,Yang Zhou,Nuo Zhou

doi:10.1186/s13765-020-00501-5

Cuiping Li, Weidong Jiang + Show 3 more

Open Access

https://doi.org/10.1186/s13765-020-00501-5

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Abstract

Platelet factor-4 variant 1 (PF4V1) was recently described as a natural non-allelic gene variant of platelet factor-4 (PF4), which has been closely associated with the growth and metastasis of various cancers. Our previous research showed that PF4V1 was related to oral squamous cells carcinoma (OSCC) metastasis. Howerver, it is still not clear about the functional role of PF4V1 in OSCC. In this study, stably transfected cell lines were constructed and the expression level of PF4V1 was verified by real‐time polymerase chain reaction (RT-PCR) and western blot. The effect of PF4V1 on proliferation, migration, invasion, and apoptosis of oral cancer (OC) cells were detected. Moreover, a xenograft tumor model was constructed to evaluate the effect of PF4V1 on OSCC in vivo. Indicators of Wnt/β-catenin, angiogenesis and epithelial-mesenchymal transition (EMT) pathways were also examined. Stable cell lines with overexpression and inhibited expression of PF4V1 were constructed successfully. After stable transfection, PF4V1 significantly promoted the proliferation, migration, and invasion of OC cells in vitro, and their tumor formation in vivo. Furthermore, PF4V1 remarkably promoted the expression of β-catenin, VEGF, and FGF but suppressed the expression of GSK-3β. There was no statistically significant correlation between PF4V1 and EMT pathway. This study provides evidence that PF4V1 promotes the proliferation, migration, invasion and tumor formation of OC cells by regulating the Wnt/β-catenin pathway and angiogenesis. Our findings suggest that PF4V1 could be a very promising target of OSCC therapy in the future.

Highlights

Oral squamous cells carcinoma (OSCC) is the 3rd and 6th most common cancer type in developing countries and worldwide, respectively [1]
The results from RTPCR and western blot showed that the overexpression and suppressed expression of Platelet factor-4 variant 1 (PF4V1) was fulfilled in SCC-9 and CAL-27 cells (Fig. 1)
Silent expression of PF4V1 inhibited the proliferation of the SCC-9 (Fig. 2b, c) and CAL-27 (Fig. 2e, g) cells when compared with the control group after incubation for 48 h and 72 h (P < 0.05)

Summary

Introduction

Oral squamous cells carcinoma (OSCC) is the 3rd and 6th most common cancer type in developing countries and worldwide, respectively [1]. Platelet factor-4 (PF4) was described as the first chemokine that inhibited neovascularization [6]. As the product of the nonallelic variant gene of PF4, platelet. Li et al Appl Biol Chem (2020) 63:18 factor-4 variant 1(PF4V1) was isolated initially from thrombin-stimulated human platelets and purified to homogeneity [6]. The difference between secreted PF4 and PF4V1 was merely three amino acids, PF4V1 had a greater potential than PF4 in inhibiting chemotaxis of human microvascular endothelial cells. PF4V1 released from activated platelets influenced angiogenesis and vascular diseases. A previous study confirmed that recombinant PF4V1 was a stronger angiostatin chemokine in inhibiting tumor growth and metastasis than PF4 in a variety of different solid tumor types [7]. Our study explored the potential of PF4V1 as an anti-tumor agent in OSCC

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