Spread of Cancer Into the Lungs Halted By Suppression of Specific Protein in Mouse Study

Spread of Cancer Into the Lungs Halted By Suppression of Specific Protein in Mouse Study

lung cancerA new study entitled “Role of Chitinase 3-like-1 and Semaphorin 7A in Pulmonary Melanoma Metastasis” reports that suppressing or decreasing the expression of Chi3l1 can significantly impair the spread of melanoma and breast cancer cells into the lungs. The study was published in the journal Cancer Research.

Melanoma, a type of skin cancer, forms from melanocytes, specialized skin cells that produce the skin-darkening pigment melanin. While melanomas account for only 4% of all skin cancers, it causes the majority of skin-cancer related deaths, with The American Cancer Society estimating 9,710 deaths in 2014. Melanoma patients’ have increased levels of a protein called Chitinase 3-like-1 (Chi3l1) in their circulation, which is associated with a poor prognosis. The expression of Chi3l1 is not restricted to malignant melanomas and is found increased in many other types of cancer and a variety of diseases, including infections and inflammatory syndromes, such as idiopathic pulmonary fibrosis and asthma. However, in melanomas the  increase of expression in Chi3l1, as well as its role in melanoma metastasis is unknown.

In this new study, a team of researchers at Brown and Yale University determined whether Chi3l1 has a functional role in melanoma progression, particularly in the formation of metastases in the lungs. The authors confirmed Chi3l1 induced expression when mice were injected with malignant melanoma cells. Additionally, to determine if Chi3l1 is important for the metastatic spread of cancers, the researchers compared the dissemination of either breast cancer and malignant melanoma cells to the lungs in both wild-type and mice lacking Chi3l1. They observed a significant decrease in lung metastasis in the “knock-out” mice for Chi3l1, when compared to the wild-type control mice. The same phenotype was observed by blocking Chi3l1 with antibodies.

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The team performed further studies and identified the regulator of Chi3l1 – the semaphorin 7a (Sema7a) protein. Mice lacking Sema7a not only expressed reduced levels of Chi3l1, as well as exhibited fewer melanoma metastases in the lungs. Specifically, they found that Sema7a by interacting with the β1 integrin protein inhibits Chi3l1, while the reverse occurs when Sema7a interacts with the plexin C1protein, leading to the production of Chi3l1.

These findings carry key potential clinical applications, with Chi3l1 as a possible key player in metastasis for other types of cancer. Accordingly, the authors encourage further studies to confirm the role of Chi3l1 in other malignancies. If indeed Chi3l1 is a fundamental key player in cancer metastasis it can become, in a near future, the target of new anti-metastatic therapies.

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