If the growth of a tumor can be compared to the construction of a building, recent research conducted by scientists from The University of Texas MD Anderson Cancer Center and The University of North Carolina at Chapel Hill (UNC) discovered a particular component that highlights this metaphor: collagen “cross-links.”
Collagen “cross-links” are protein complexes responsible for the link between “stroma” tissue cells and their ability to both stiffen and stimulate the invasion and metastasis of tumor cells. The researchers compared tumor growth to the construction of a skyscraper, due to a tumor’s biological matrix, which enables it to thrive and spread.
The study, which was recently published in the Journal of Clinical Investigation, revealed that while collagen is among the most typical kind of scaffolding protein, responsible for the strengthening of tissues, its metabolism does not work normally in cancers originating in epithelial tissues. This particular field has been widely studied, however, these new findings are thought to have increased the current knowledge of cancer cells’ invasion capacity.
The research team, led by Mitsuo Yamauchi, Ph.D., analyzed two collagen cross-links: hydroxylysine aldehyde-derived collagen cross-links (HLCC) and lysine aldehyde-derived collagen cross-links (LCC) in both mice and human epithelial lung cancer specimens. They concluded that it is more common to find HLCCs in skeletal tissues compared to LCCS, which are commonly present in soft tissues.
“We observed that tumor stroma had higher amounts of HLCC and lower amounts of LCC than what is found in normal tissue,” explained professor Jonathan Kurie, M.D., from the department of Thoracic/Head and Neck Medical Oncology, in a press release. “Expression of the gene LH2 or lysyl hydroxylase 2 in tumor cells increased the HLCC-to-LCC ratio in tumor stroma and enhanced tumor stiffness leading to metastasis. These findings suggest that the types of collagen cross-links in cancer may play a crucial role in regulating stromal stiffness and determining tumor cell metastatic fate.”
Therefore, the researchers came to recognize that LH2’s ability to activate cancer cells and metastasize makes it work as a regulatory “switch,” and consequently LH2 can regulate the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. “Our investigation presented the first evidence that the types of collagen cross-links in tumor stroma are important in determining stromal stiffness and tumor cell metastatic potential,” added Kurie.
Jonathan Kurie was one of the two prominent lung cancer researchers from the University of Texas MD Anderson Cancer Center who were chosen to be included on a list of sixteen researchers nationwide and granted $800,000 awards from the Lung Cancer Research Foundation.