Fatty liver suppressed the angiogenesis in liver metastatic lesions

We have demonstrated that colorectal cancer with fatty liver had few liver metastases clinically as well as experimentally. In this study, to clarify why colorectal cancer with fatty liver had few liver metastases, we focused on the angiogenesis of carcinomas.

The rat colon cancer cells (RCN-9) were injected into 40 rats (the fatty liver group = FL group includes 20 rats, the non-fatty liver group = NFL group includes 20 rats). In each group, the PyNPase (pyrimidine nucleoside phosphorylase) activity in the metastatic lesion of the liver was examined using the high-performance liquid chromatographic method. In addition, the microvessel density in the metastatic lesion of the liver was assessed by Von Willebrand factor-related antigen immunostaining.

1) The PyNPase activity in the FL group was 33.34 +/- 6.27 (microgram FU/mg protein/hr), which was significantly lower than that of the NFL group (49.30 +/- 14.82) (P = 0.0021). 2) Microvessel density in the FL group was 1.845 +/- 0.357 (%), while that in the NFL group was 2.777 +/- 1.371 (%). The microvessel density of the FL group was significantly lower than that of the NFL group (P = 0.0365). 3) The regression coefficient between PyNPase activity and microvessel density was 0.480, which indicated a significant correlation (P = 0.0098).

We think that, in colorectal carcinomas with fatty liver, the decreased activity of PyNPase and the decreased neovascularization in the metastatic lesion are closely related to fewer liver metastasis compared with colorectal cancer patients without fatty liver.