Drug Increases Collagen in Melanoma Cells

Uncertainty persists in how collagen influences cancer cell behavior.

A common cancer drug was found to increase collagen in the cells of melanoma, which has a still undetermined effect on cell behavior, a recent study found.

The presence of collagen in the tumor microenvironment can be either positive or negative, according to a study published recently in in Matrix Biology Journal. The study found that the BRAFV600E inhibitor PLX4032 (Vemurafenib) increases type 1 collagen synthesis in melanoma cells.

"Vemurafenib usually suppresses expression of genes in melanoma cells," study lead Constance Brinckerhoff, PhD, said in a press release. "Surprisingly, we found that expression of collagen was substantially increased by melanoma cells treated with this drug."

Vemurafenib, which is a common treatment for melanoma patients with a BRAF gene mutation, was evaluated to determine its effect on tumor cell collagen synthesis.

The researchers found Vemurafenib inhibits the expression of numerous genes, however just a few genes were upregulated by the drug. The ability of Vemurafenib to increase collagen expression was both surprising and potentially innovative, according to the study.

Investigators will next test the drug in mice to evaluate whether increased collagen deposition has a positive or negative impact. Prior research on the subject is in conflict, as some studies indicated collagen synthesis helps the tumor, as other findings suggest collagen has a negative impact on tumors.

The researchers said they next hope to determine whether Vemurafenib, inhibits tumor progression, or if that is an off-target effect.

"Our findings were replicated in 3 melanoma cell lines and in murine melanoma cells that are a model for human disease," Dr. Brinckerhoff said. "They were also replicated with in vivo experiments where mice harboring melanomas were fed chow with or without the drug and we also saw increased collagen in the tumors in these mice."