The relationship between angiogenesis and tumor cell apoptosis in colorectal cancer

Angiogenesis is 1 of the 6 cellular transformations that lead to malignant growth^1,2

Hanahan and Weinberg proposed that most, if not all, human cancers share 6 acquired capabilities that enable malignant growth. These traits include self-sufficiency in growth signals, insensitivity to growth-inhibiting signals, evasion of apoptosis, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. This last capability, angiogenesis, enables tumor cells to obtain the oxygen and nutrients they need to grow, and is regulated by a complex system of cellular signals.¹

Reprinted from Hanahan D, Weinberg RA, "Hallmarks of Cancer: The Next Generation" in Cell, 2011;144:646-674, with permission from Elsevier.

Resisting cell death and inducing angiogenesis are 2 of the 6 "Hallmarks of Cancer" described by Hanahan and Weinberg.^1,2 These 2 tumor traits are interrelated through a number of complex cellular mechanisms, including Bcl-2, and other cell death–regulating pathways. In an analysis of 44 adenomas and 26 carcinomas, Aotake and colleagues observed a significant correlation between tumor cell apoptosis and angiogenesis. The investigators noted that microvessel density gradually increased as cancer progressed (ie, from low dysplasia to high dysplasia to carcinoma). Further analysis revealed an inverse relationship between microvessel density and the apoptotic index (ie, the percentage of apoptotic cells in a given specimen of tumor cells). The authors concluded that angiogenesis is a key factor in colorectal cancer progression and, further, that angiogenesis may cause a reduction in tumor cell apoptosis over the course of development.³

Relative VEGF expression levels in Dukes' Stage C colon cancer and surrounding mucosa⁴

Kuniyasu et al measured VEGF expression in colon cancer. Median intensity of VEGF expression was quantified in distant mucosa (control), adjacent mucosa, and tumor tissue, with a value of 100 assigned to the control. Adjacent mucosa and tumor tissue had comparatively higher intensities of VEGF expression, with values of 209 and 227, respectively (P<0.0001).⁴

Adapted from Kuniyasu 2000.

VEGF: expressed at elevated levels in malignant cells

In an analysis of colon cancer surgical specimens, Kuniyasu and colleagues found elevated vascular endothelial growth factor (VEGF) levels in tumors and adjacent mucosa compared with distant mucosa in all of Dukes' Stage C (n=34) carcinomas. In Dukes' Stage B (n=40) carcinomas, elevated VEGF levels were observed in all tumors compared with distant mucosa.⁴

References:

1.

Hanahan D, Weinberg RA. Cell. 2000;100:57-70.

2.

Hanahan D, Weinberg RA. Cell. 2011;144:646-674.

3.

Aotake T, Lu CD, Chiba Y, et al. Clin Cancer Res. 1999;5:135-142.

4.

Kuniyasu H, Yasui W, Shinohara H, et al. Am J Pathol.
2000;157:1523-1535.