Tumor blood vessels can develop from precancerous stem cells, a new study has shown.
The precancerous stem cells are the recently discovered type of cell that can either remain benign or become malignant.
Tumors require a blood supply to grow, but how they acquire their network of blood vessels was not clearly understood up till now.
The study, led by Jian-Xin Gao, assistant professor of pathology at the Ohio State University Comprehensive Cancer Center and Department of Pathology, stated that the findings provide new information about how tumors develop blood vessels, and why new drugs designed to block tumor blood-vessel growth are often less effective than expected.
"These findings suggest that tumor blood vessels are derived mainly from tumor cells, with a smaller number coming from normal blood-vessel cells. This may explain why many anti-angiogenic drugs fail to block tumor growth," Gao said.
Gao contemplated that the potential anti-angiogenic drugs are usually screened using normal blood-vessel cells, also called endothelial cells, or their progenitors.
"The screened drugs may be very good at blocking the formation of blood vessels made by normal endothelial cells, but have little effect on blood-vessel formation by precancerous stem cells or other blood-vessel-forming cancer cells. Our findings suggest that screening of these agents should include precancerous stem cells," Gao said.
In the study, the research team used mouse precancerous stem cells grown in the laboratory and transplanted into immune-deficient mice. The researchers removed the resulting tumors from the mice and, using tests for various molecular markers, observed that the tumor blood vessels were largely derived from precancerous stem cells.
"The tumor blood-vessel cells were abnormal and highly variable in appearance compared with normal cells," Gao said.
The precancerous stem cells also produced similar levels of substances that stimulate blood-vessel growth i.e., angiogenic factors, but they were much more potent in forming new blood vessels and larger tumor masses compared with tumors grown from typical tumor cells.
The researchers examined new blood vessel formation in human tumors transplanted into mice, and observed changes similar to those previously seen in the mouse tumors.
The researchers, then, examined the appearance of blood vessels in human cervical and breast tumors and observed that the blood-vessel cells displayed similar abnormalities and aberrant patterns of molecular markers.
"This suggests that the ability of these tumors to form blood vessels is likely linked to precancerous stem cells or other blood-vessel-forming tumor cells," Gao said.
The study is published in the journal PLoS ONE.