Platelet lysates in Hepatocellular Carcinoma patients after radiofrequency ablation facilitate tumor proliferation, invasion and vasculogenic mimicry

Abstract

Background: Platelets play important roles in tumorigenesis, angiogenesis and metastatic dissemination of tumor cells. Radiofrequency ablation (RFA) could increase the circulating tumor cells in patients with primary or metastatic lung tumors. Whether platelet lysates in hepatocellular carcinoma (HCC) after RFA promote tumor progression has not been elaborated. Methods: HCC patients within Milan Criteria and without taking anti-platelet drugs were selected in the study. MTT assay, colony formation assay, transwell assay, tube formation and western blot were used to evaluate the effect of platelet lysates on HCC cells in vitro. Lung metastatic assay was performed in vivo. Results: Platelet lysates from patients after RFA promoted cell proliferation, colony formation, migration, invasion and vasculogenic mimicry in Hep3B and HCCLM3 cells compared with those from patients before RFA. Platelet lysates after RFA significantly increased the expression of p-Akt, p-Smad3 and snail, and decreased the expression of E-cadherin compared with those before RFA in Hep3B and HCCLM3 cells. Hep3B-Luc2-tdT cells incubation with platelet lysates from patients after RFA displayed enhanced lung metastasis compared with those before RFA. Conclusions: Platelet lysates from HCC patients after RFA promoted the proliferation, migration, invasion and vasculogenic mimicry of HCC cells, which indicated that RFA in combination with anti-platelet drug may be used to improve the prognosis of HCC.

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research

“…Cancer stem cells and EMT participate in VM (65). Jia et al (66) found that platelet lysates in patients with HCC after RFA can promote EMT and activation of Akt, ERK1/ 2 and Smad3 signals, further promoting tumor VM and metastasis of HCC after RFA. Kong et al (44) also demonstrated that EMT participated in VM and promoted progression of HCC after insufficient RFA.…”

“…Kong et al (63) found that ICAM-1 activates platelets in residual tumor tissue after RFA and promotes vascular permeability in TAECs via VE-cadherin and that anti-platelet and anti-ICAM-1 therapy could prevent progression of HCC after RFA. Furthermore, Jia et al (66) compared the effect of platelet lysates in HCC cell lines before and after RFA and found that lysates obtained from patients after RFA of HCC could promote proliferation, migration, invasion, and VM of HCC cells. They also demonstrated that platelet lysates from patients who had undergone RFA accelerated metastasis of HCC cells to the lung.…”

“…Jia et al. ( 66 ) found that platelet lysates in patients with HCC after RFA can promote EMT and activation of Akt, ERK1/2 and Smad3 signals, further promoting tumor VM and metastasis of HCC after RFA. Kong et al.…”

“…Furthermore, Jia et al. ( 66 ) compared the effect of platelet lysates in HCC cell lines before and after RFA and found that lysates obtained from patients after RFA of HCC could promote proliferation, migration, invasion, and VM of HCC cells. They also demonstrated that platelet lysates from patients who had undergone RFA accelerated metastasis of HCC cells to the lung.…”

Platelets are highly efficient and efficacious carriers for tumor-targeted nano-drug delivery

“…Platelets can be recruited to the tumor microenvironment (TME) to bolster cancer proliferation through release of mitogenic factors. Platelets also act in concert with other immune cells in the TME to create an immunosuppressive microenvironment that promotes therapy resistance (D'Alessandro et al., 2015 ; Huijbers et al., 2016 ; Schlesinger, 2018 ; Xu et al., 2018 ; Jia et al., 2020 ). Moreover, platelets can form aggregates with metastatic cancer cells in the blood stream and thereby protect the cancer cells from the attack by blood shear forces and circulating immune cells.…”