A new study from Finland sheds new light on how melanoma cells interact with other cells through the extracellular vesicles they secrete. The researchers found that extracellular vesicles secreted by melanoma cells use the so-called hedgehog signaling pathway to intensify the malignant properties of the cells to which they are directed. The discovery can help in the development of a better treatment and diagnosis for melanoma. Published in Cellular and molecular life sciences, the study was carried out in collaboration between researchers from the University of Eastern Finland and the University of Helsinki.
Many of the mechanisms that regulate the function of our body have remained unchanged throughout evolution. This means that the same genes regulate the development and function of all multicellular animals. An example of such genetic survival is the so-called hedgehog signaling pathway. The family of genes associated with this signaling pathway receives its unique name from a mutation that caused the larvae of the fruit fly, making them appear pointed, like a hedgehog. The most common of the three hedgehog genes found in mammals, the Sonic hedgehog gene, is named after the famous videogame character. In mammals, members of the hedgehog family of genes are essential regulators of fetal development, but they are also associated with the division of stem cells at later stages of development and even in adults. Recent studies suggest that its expression is also associated with many different types of cancer, including skin cancers. Melanoma is the most serious form of skin cancer and is becoming increasingly common.
Extracellular vesicles carry signals between cells, and can also transport packaged medications.
Traditionally, it is believed that signaling in the body is done through free circulation signals, such as growth factors and hormones. However, according to a more recent opinion, it is believed that some signals are packaged for transport in order to protect them from breakage and ensure their delivery to the correct address. Extracellular vesicles are small bubble-shaped packets made of cell membrane, which serve as natural carriers of signals in the body. They regulate the function of the body already during the fetal stage, through breast milk and also later in life as our tissue regenerates. Cancer cells also use extracellular vesicles to send signals and modify their environment, which makes it favorable for growth. Extracellular vesicles can also be used as various drug carriers to fight disease and repair tissue damage, and that is why they are being studied so actively at this time.
In the recently published study, researchers discovered a new link between extracellular vesicles and hedgehog molecules. They discovered that the vesicles secreted by melanoma cells intensify the malignant properties of the cells to which they are directed, such as division and spread, through the hedgehog signaling pathway. The researchers used cultured human melanoma cells and normal skin cells, confirming their cell culture findings by analyzing tissue samples from melanoma patients.
It is a coincidence that these signal-carrying vesicles originate from cells that are also known as hedgehog cells due to their small spike-shaped microscopic protuberances. However, these bumps have nothing to do with the fruit fly larvae; instead, they are typically found in cells that are active in the production of hyaluronan, the most common sugar molecule in the extracellular matrix. The hyaluronan also plays a key role in vesicle-mediated signaling, since the hyaluronan found on the surface of the vesicles protruding from the cell surface facilitates its binding to the target cell. “
Docent Kirsi Rilla, University of Eastern Finland
The hedgehog signaling pathway is very promising as a goal for drug therapy in melanoma and other types of cancer. The regulatory mechanism now discovered by researchers can be used in the development of better diagnoses and drug therapy for patients with melanoma.
The Docent Rilla research group has been studying the biology of extracellular vesicles since 2013.
Eastern Finland University
Arasu, U. T., et al. (2019) The HAS3-induced extracellular vesicles of melanoma cells stimulate the positive regulation of IHH-mediated c-Myc through the hedgehog signaling pathway in the target cells. Cellular and molecular life sciences. doi.org/10.1007/s00018-019-03399-5.