Prokineticin 2 (PROK2) is an important factor for angiogenesis in colorectal cancer

Abstract

The Prokineticin 2 (PROK2) is correlated with indispensable in maintaining the homeostasis of healthy human tissues. Herein, we examined the role of PROK2 in human colorectal cancer.After total RNA extraction from 6 colorectal cancer cell lines, we examined the expression of PROK2 mRNA. For investigating angiogenesis and tumor growth in mice, the PROK2 gene was transfected into colorectal cancer cell lines having low PROK2 mRNA expression. In addition, small interfering RNA (siRNA) was transfected into colorectal cancer cell lines having high PROK2 mRNA expression for investigation of angiogenesis and tumor growth in mice.From 6 colorectal cancer cell lines studied, PROK2 mRNA expression was increased in 3 cell lines. When the PROK2 gene was transfected into the colorectal cancer cell line with low PROK2 mRNA expression, angiogenesis and tumor growth in mice increased significantly compared to the cell line with the control vector.When PROK2 siRNA was transfected into colorectal cancer cell lines with high PROK2 mRNA expression, angiogenesis and tumor growth in mice were suppressed significantly compared to the cell line with siRNA (control). This is the first report of the association of PROK2 as an angiogenic growth factor in colorectal cancer.

Prokineticin 2 expression as a novel prognostic biomarker for human colorectal cancer

“…Previous reports have demonstrated that inflammatory cytokines affect the microenvironment of existing cancer cells and facilitate the migration, invasion, and angiogenesis of cancer cells [ 35 , 36 ]. The findings of our present and previous study [ 21 ] show that PROK2 expression is highly correlated with angiogenesis, tumor formation, and liver metastasis through in vitro and in vivo assays. This suggests that in CRC, the tumor itself organizes the surrounding environment via PROK2 expression, which plays a significant role within the tumor microenvironment.…”

“…The primer sequences for PROK2 (GenBank accession no. NM_021935) gene-coding regions were as follows: 5′ primer, PROK2-AX: 5′-GGGGATCCATGAGGAGCCTGTGCTGCGCCCCA-3′; 3′ primer, PROK2-BX: 5′-GGGAATTCCTTTTGGGCTAAACAAATAAATCG-3′ [ 21 ]. GAPDH was used as an internal PCR control.…”

“…These findings highlight the relationship of PROK2 with malignant tumors. Our previous study found that PROK2 expression is associated with angiogenesis and tumor formation in CRC [ 21 ]. However, the prognostic value of PROK2 expression in human CRC remains unclear.…”

Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression

“…Use of PROK2 antagonist suppresses the tumorigenic processes through inhibiting angiogenic process in glioma and blocking myeloid cell infiltration in pancreatic cancer [ 10 ]. Colorectal cancer cells with PROK2 siRNA show a significant decrease in PROK2 expression and tumor growth in mice models [ 11 ]. MicroRNA-374a acts as tumor suppressor to inhibit cell proliferation, cell cycle progression, and cell invasion through targeting PROK2 in human glioma cells [ 19 ].…”

“…Prokineticin 2 (PROK2), a member of prokineticin protein family, is a cysteine-rich secreted protein containing a conserved N-terminal sequence of AVITGA and 10 cysteines [ 9 ]. Studies have shown that PROK2 might be involved in tumorigenic processes through regulating angiogenesis in glioblastomas [ 10 ] and in colorectal cancer [ 11 ], myeloid cell infiltration in pancreatic cancer [ 12 ], growth in hepatocellular carcinoma [ 13 ] and tumor progression in prostate cancer [ 14 ]. PROK2 might be related to drug resistance of breast cancer and metastasis to lung [ 15 ].…”