Colorectal cancer commonly metastasizes to the liver and is the second leading cause of death from cancer in the United States. As with most cancers, it is the metastasis and not the primary tumor that is responsible for cancer fatality. However, the complex mechanisms associated with tumor metastasis are not very well understood. Dr. Xiao-Fan Wang from Duke University Medical Center and colleagues searched for genes associated with metastatic tumors in samples from primary and metastatic colon cancers and found that periostin was highly expressed in metastatic tumors. When periostin was introduced into human colon cancer cells grown in the laboratory, the cells were much more likely to metastasize to the liver when subsequently introduced into mice. The researchers went on to show that the underlying molecular mechanism for periostin-mediated tumor metastasis is related to an increase in survival of cancer and blood vessel cells under stressful conditions.
The researchers conclude that periostin plays a critical role in the progression of colon cancers and may be involved in metastasis of other cancers as well. "Metastasis accounts for the majority of the mortality associated with colorectal cancer, making control of metastasis an attractive treatment goal," explains Dr. Wang. "Our findings identify periostin as a potent promoter of late stage tumor progression. It is likely that periostin and similar types of proteins enable tumor cells to thrive in distant organs and grow under conditions that normally would be inhospitable. Targeting these proteins may prove to be a highly effective strategy for preventing late-stage progression of deadly metastatic cancers."
Shideng Bao, Gaoliang Ouyang, Xuefang Bai, Zhi Huang, Chaoyu Ma, Ming Liu, Rong Shao, Ryan M. Anderson, Jeremy N. Rich, and Xiao-Fan Wang: "Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway"
Published in Cancer Cell, Volume 5, Number 4, April 2004.
Journal
Cancer Cell