《自然》：人类皮肤可以拒绝肿瘤并自愈

《自然》：人类皮肤可以拒绝肿瘤并自愈

Nature: Our skin's ability to reject tumors and heal itself

One in every 3 cancers diagnosed worldwide is a skin cancer. Yale researchers revealed in Nature this week their new discoveries about how our skin naturally resists tumor formation. But how will this lead to a treatment? Perhaps the calcium flux of skin cells is the next step for this research.

The Paper

Nature published this week; "Correction of aberrant growth preserves tissue homeostasis," by Samara Brown and Cristiana M. Pinedain Dr. Valentina Greco's lab at Yale University. They explored the skin's mechanisms of recognizing and defeating mutated cells, by looking at the behavior of the surrounding healthy cells.

These scientists engineered some hair-follicle stem cells to overexpress βcatenin, a cell proliferation protein, in a mouse model. They used fluorescence microscopy to view the hair follicle cells over several weeks. They found that the mutant cells grew into small cysts as expected, but the healthy neighboring skin cells responded by increasing their own rate of growth, defeating the mutant cells and leading to complete regression of the cysts.

Their initial introduction of mutated cells was just enough to mimic common mutations that arise in skin, but after seeing the quick regression, they decided to challenge the tissue. They introduced larger numbers of mutated cells, and within three weeks, saw several moderate sized, but benign tumors. Amazingly, by 4 months after induction, those tumors were gone; the healthy skin tissue successfully eliminated full tumors.

This research points to exciting possibilities of finding possible cancer treatments within our own cells. However, this phenomenon needs to be better understood, so more research is needed. What else could be studied in skin cells to further this research?

NMT Connection

Calcium is an important signaling molecule in many forms of life, but in skin cells, it has been long known to have an effect on cell proliferation. According to a paper published in Cell in 1980 by Henry Hennings and Stuart Yuspa from the US National Cancer Institute, change in concentration of Ca2+ ions can strongly alter the patterns of growth and differentiation of cultured mouse epidermal cells. They found that decreasing Ca2+ concentration greatly increased proliferation, and bringing Ca2+ levels back up slowed growth.

This mechanism of calcium signaling in skin cells has long been known, and new technology will allow us to take advantage of this knowledge and apply it to new discoveries. Using the non-invasive micro-test technology (NMT), researchers could measure the calcium flux in the rapidly growing healthy cells that push out cancer, and see if the change in calcium flux and cell growth are linked. These flux data could also be compared to the calcium flux in the mutated cells, to reveal if their proliferation is affected by calcium as well.

Dr. Greco's team at Yale have made exciting insights about the amazing power of human skin to eliminate tumors and mutations. More research on this phenomenon and its accompanying factors like calcium signaling may be right around the corner.

References:

S. Brown, C. M. Pineda, et al. Correction of aberrant growth preserves tissue homeostasis. Nature 2017. 548:334–337 doi:10.1038/nature23304

H. Hennings, D Michael, et al. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 1980. 19:245–254.