Prokineticin-1 induces normal lymphangiogenic activity and is involved in lymphangiogenesis and lymph node metastasis in colorectal cancer.

Takayuki Naruse,Akio Yamaguchi,Takanori Goi

doi:10.18632/oncotarget.28016

Abstract

Background: Prokineticin family correlates with important roles in several biological processes, including homeostasis. We discovered novel functions of prokineticin1 (PROK1) in lymphangiogenesis and lymphnode metastasis in colorectal cancer.Materials and Methods: We examined changes in the number of lymphatic endothelial cells after PROK1 stimulation. PROK1 protein was stimulated with subcutaneously implanted in mice. Also a high-PROK1-expressing colorectal cancer cell line and anti-PROK1 antibody(Ab) were subcutaneously implanted in mice, and then examine lymphangiogenesis. PROK1 expression and the number of lymph vessels were examined in the primary lesion of 391 patients whose colorectal tumors had been resected.Results: When PROK1 was used as a stimulus, the number of lymphatic cells increased compared to unstimulated cells. And the number of lymph vessels in the skin of mice increased compared to mice implanted without PROK1. The number of lymph vessels in the primary tumor tissue increased when PROK1 was highly expressed compared to cases with non-detectable PROK1 expression. When PROK1 was expressed in human colorectal tumors, the rate of lymphnode metastasis was significantly higher than that in cases with non-detectable PROK1 expression.Conclusions: PROK1 is a lymphangiogenic factor involved in the formation of new lymph vessels and lymphnode metastasis in human colorectal cancer.

Highlights

The morbidity rate for colorectal cancer is very high in Japan and in western countries [1,2]
PROK1 is a lymphangiogenic factor involved in the formation of new lymph vessels and lymphnode metastasis in human colorectal cancer
We identified a new relationship between PROK1 expression and lymphatic formation, invasion, and metastasis in human colorectal cancer

Summary

Introduction

The morbidity rate for colorectal cancer is very high in Japan and in western countries [1,2]. While the use of anticancer and molecular-target drugs for unresectable colorectal cancer has improved its survival rate [3,4,5], this type of cancer has not yet been eradicated, and further countermeasures are needed. Hematogenous, lymph node, and peritoneal metastases often occur, and are important factors for tumor progression and adequate prognosis [6, 7]. Elucidation of the mechanisms driving metastasis in colorectal cancer can improve the prognosis of patients and expedite the development of new therapeutic strategies. Lymphangiogenesis is considered an important factor for the development of lymph node metastases. Prokineticin family correlates with important roles in several biological processes, including homeostasis. We discovered novel functions of prokineticin (PROK1) in lymphangiogenesis and lymphnode metastasis in colorectal cancer

Methods

Results

Discussion

Conclusion