Melanoma Deadlier in Men Due to Age-Related Changes in Their Fibroblasts

Source: Geneng News, September 2024

The results of newly reported research in human cells and in mice, carried out by scientists at Johns Hopkins Kimmel Cancer Center, suggest that age-related changes in fibroblasts contribute to the development of aggressive, treatment-resistant melanoma in males. The researchers, co-led by Ashani Weeraratna, PhD, the Bloomberg Distinguished Professor, E.V. McCollum Professor, and chair of the department of biochemistry and molecular biology at Johns Hopkins, found that human skin fibroblasts—cells that create the skin’s structure—show age-and sex-specific changes in proliferation and stress response, and that male fibroblasts age faster due to elevated levels of reactive oxygen species (ROS).

The studies in addition indicated that bone morphogenetic protein 2 (BMP2) is secreted in the aged male dermal microenvironment, and this promotes invasive melanoma that is resistant to BRAF/MEK inhibition. Further investigation showed that inhibiting BMP2 activity blocked development of this invasive tumor phenotypes and sensitized the melanoma cells to BRAF/MEK inhibition.

Reporting on their studies in Cell, “Sex-dependent effects in the aged melanoma tumor microenvironment influence invasion and resistance to targeted therapy,” the team, co-led by Yash Chhabra, PhD, currently an assistant professor at Fox Chase Cancer Center in Philadelphia, stated, “Understanding sex differences in melanoma and intrinsic cellular changes with age will aid in identifying new pharmacological vulnerabilities toward personalized therapies that influence both tumor aggressiveness and treatment response.”
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