In a recent study published in the Journal of Clinical Investigation, researchers at The University of Texas MD Anderson Cancer Center and The University of North Carolina at Chapel Hill (UNC), revealed that distinct collagen links can determine the growth and spread abilities of cancer. The study is entitled “Lysyl hydroxyls 2 induces a collagen cross-link switch in tumor stroma.”
It is known that collagen metabolism is affected in cancers derived from epithelial tissues, such as epithelial lung cancer. Collagen is a common type of support protein, providing tissue strength. Researchers now found that collagen “cross-links” are determinant for a tumor’s ability to grow and spread, as they allow connective tissue cells (also called stroma) to harden, stimulating tumor cell invasion and metastasis.
Two collagen cross-links were assessed in the study: LCC (lysine aldehyde-derived collagen cross-links) and HLCC (hydroxylysine aldehyde-derived collagen cross-links), and both were analyzed in human epithelial lung cancer tissues and in metastatic lung cancer mouse models. HLCCs are predominantly found in skeletal tissues, whereas LCCs are usually present in soft tissues.
The research team found that an enzyme called lysil hydroxyls 2 (LH2), which catalyzes the hydroxylation of lysine to hydrolysine, was expressed in tumor cells, resulting in an increase of HLCC when compared to LCC in the tumor stroma. “We observed that tumor stroma had higher amounts of HLCC and lower amounts of LCC than what is found in normal tissue,” said the study’s senior author Dr. Jonathan Kurie 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.”
LH2 was found to be a regulatory “switch” able control the abundance of specific types of collagen cross-links in the tumor stroma and enhance the capacity of tumor cells to form metastasis. LH2 can be considered an indicator of poor prognosis in lung cancer patients. The team believes that the activity of LH2 can be selectively inhibited, opening a potential new therapeutic strategy for halting the growth and spread of epithelial cancer.
“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,” concluded Dr. Kurie.