Study Strengthens Argument of Cancer as "Wounds that
Do Not Heal"
A recent study provides new evidence that some types of cancer may have similarities with wound healing, demonstrating that during both processes many of the same genes are regulated in a coordinated manner.
However, the study also revealed distinct gene expression patterns, or signatures, that appear to represent the point where the two processes diverge.
This study is the first to compare and analyze the gene expression patterns of renal cell carcinoma (RCC) and gene expression during recovery from ischemia-induced damage to the kidney (renal wound healing). The study was led by Dr. Joseph Riss of the Laboratory of Biosystems and Cancer in NCI's Center for Cancer Research.
The suggestion that cancer and wound healing share many features of the same biological process dates back to the early 1970s, Dr. Riss explained.
In the July 15 Cancer Research, Dr. Riss and colleagues provide a comprehensive investigation of this hypothesis. They created a mouse model of renal wound caused by a period of impaired blood flow to the kidney. Then, using microarray technology, they performed gene expression analyses several times after normal blood flow was reestablished and the damaged organ began to heal.
They compared these results with gene expression patterns of human RCC reported in the literature. They found that, relative to a normal kidney, there were 361 genes differentially expressed in both renal carcinoma and during recovery from ischemia. Of these 361 genes, 77 percent were found to be "concordant;" that is, either upregulated or downregulated in both RCC and during recovery from ischemia. The remaining 23 percent were "discordant" in that their differential expressions were in opposite directions relative to a normal kidney.
A careful gene analysis pointed to molecular pathways and gene functions involving the concordant and discordant sets.
Important orchestrated processes such as regeneration, DNA replication (e.g., MCM gene family), cell adhesion (e.g., ICAM1 and VCAM1), and immune response were reflected in the concordant genes.
The discordant gene signature revealed processes such as morphogenesis and glycolysis, and molecular pathways, such as the hypoxia-inducible factor and insulin-like growth factor-I, "that reflect the intrinsic pathologic nature of RCC," according to Dr. Riss.
"Our observations provide a conceptual framework for further efforts to understand the biology of renal regeneration and renal cell carcinoma," he continued.
"They also provide information for the development of more effective diagnostic biomarkers and therapeutic strategies for renal tumors, as well as strategies for improving recovery from renal ischemia without promoting renal cell carcinoma," he said.
By Carmen Phillips