Researchers have been trying to identify the cells at the origin of cancer and to understand the molecular changes that occur in tumour-initiating cells from the first oncogenic mutation to the development of invasive cancer. The most diagnosed cancer in humans is basal cell carcinoma, with over a million such cases reported each year. A European-funded team of researchers has finally uncovered the cells at the origin of basal cell carcinoma. 

A European Research Council (ERC) Starting Grant worth EUR 1.6 million was awarded to Professor Cédric Blanpain of the Université libre de Bruxelles (ULB). The finding was recently presented in the journal Nature Cell Biology. 

Professor Blanpain led a team that dissected for the first time the molecular changes occurring in basal cell carcinoma-initiating cells from the first oncogenic mutation to the development of invasive cancer. 

Khalil Kass Youssef, the lead author of the study, and colleagues discovered that the cells at the origin of the basal cell carcinoma were initially reprogrammed into embryonic hair follicle progenitor-like fate before they progressed into invasive carcinoma. ‘We were extremely surprised to see that tumor initiating cells were progressively and profoundly reprogram into a molecular identity that resemble to progenitor cells presented during embryonic development,’ said Dr Youssef. 

The scientists showed that the Wnt/beta-catenin signalling pathway is activated in basal cell carcinoma-initiating cells just after oncogene expression. The team established that Wnt/beta-catenin signalling is needed for the reprogramming of tumour-initiating cells into embryonic hair follicle progenitors and for tumour initiation after using genetic or pharmacologic inhibition of the Wnt/beta-catenin signalling. 

Professor Blanpain’s team, which worked together with physicians from the Department of Dermatology, Pathology and Plastic Surgery at the Hospital Erasme, indicated that human basal cell carcinomas also show signs of reprogramming into embryonic hair follicle progenitors and activating of the Wnt/beta-catenin signalling. Their discovery confirmed how important this pathway is for human patients. 

‘I am particularly excited about this work, because this basic research turns out to be very relevant for human diseases, with the identification of potentially new avenues to treat or to prevent the occurrence of the most common cancer in humans,’ said Professor Blanpain. 

This research study will help develop other work in cancer, development and stem cell biology. 

Other funding for this study came from the Fonds de la Recherche Scientifique (FNRS), the program d’excellence CIBLES of the Wallonia Region, a research grant from the Fondation contre le Cancer, the Fondation ULB, the Fonds Yvonne Boël, the Fond Gaston Ithier and the EMBO Young Investigator Programme.

For more information, please visit: 

Université libre de Bruxelles: 
http://www.ulb.ac.be/ulb/presentation/uk.html 

Nature Cell Biology: 
http://www.nature.com/ncb/index.html

Wrinkles, dryness and a translucent and fragile appearance are hallmarks of old skin, caused by the natural aging of skin cells. But while most of us can recognize the signs of lost youth when we peer into the mirror each morning, scientists do not have a standardized way to measure the extent of age damage in skin. Now, a group of Taiwanese researchers have used a specialized microscope to peer harmlessly beneath the skin surface to measure natural age-related changes in the sizes of skin cells.

This series of harmonic generation microscopy images shows the skin cells of a 24-year-old subject at increasing depths, ranging from the outermost layer of skin (a) to approximately 300 millionths of a meter deep (f). The magenta areas, generated from third harmonics, show skin cells and their nuclei. The green areas, generated from second harmonics, show fibers made of the protein collagen. (Credit: Biomedical Optics Express)

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As we get older, the trillions of cells in our body do too. And like us, they become less resilient and able to weather the stress of everyday life. Our skin especially tells the tale of what’s happening throughout our bodies.

But recently, scientists have learned that aging cells bear only part of the blame for this downward spiral. And a new study shows that it might be possible to slow the decline of aging tissue - and even make it act younger — by focusing on the stuff that surrounds those cells.

In an independent study at the University of Michigan Medical School, skin scientists have succeeded in making the skin cells of senior citizens act like younger cells again, simply by adding more filler to the fiber-filled area around the cells.

This extracellulal matrix, or ECM, acts like the scaffold that skin cells roost in. It’s made of tiny fibrils of collagen, produced by the cells (fibroblasts). Over time, as skin ages, the ECM becomes fragmented, which causes cells to lose their connections to that scaffold - and the lack of support accelerates their decline further. The same thing may happen in other types of tissue.

In the new study, scientists from the U-M Department of Dermatology injected the skin of 21 volunteers in their 80s with a filler often used cosmetically to reduce facial wrinkles. The filler bolsters the ECM, filling in the spaces left by aging.

The researchers did not receive funding from the product’s manufacturer, nor did they get input on the design or results from the company. Rather, they were using the product as a way to increase the mechanical forces within the volunteers’ skin.

They also didn’t focus on the face, where skin takes a beating over a lifetime of exposure to ultraviolet light and other insults that break down collagen. Instead, they focused on skin that had almost never seen the light of day - the buttocks.

The result: over three months, the fibroblasts began expressing collagen-related genes, producing more collagen, and connecting better to the ECM. The entire layer of skin grew thicker, and more blood vessels, which nourished the cells were seen. READ MORE 

Source: University of Michigan Health System

Fish oil supplementation was associated with improvement of inflammatory acne, especially in patients with moderate to severe acne, according to study results. READ MORE 

(Source: healio.com)

The researchers investigated the genes of marine creatures, such as sea urchins and sea cucumbers, known as echinoderms. They found the genes for “messenger molecules” known as peptides, which are released by cells and tell other cells in their bodies what to do. The study was published online in the journals PLOS One and General and Comparative Endocrinology. Read MORE 

(via Queen Mary, Univeristy of London via Phys.Org)

Alpha hydroxyl acids (AHA’s) are an important ingredient in a lot of cosmetic products including wrinkle-reducing creams and chemical peels, but until recently, scientists really didn’t understand how AHA’s really worked. Though no one could dispute the fact that these products did encourage the exfoliation and new growth of skin to enhance appearance, the actual chemical and physiological basis for their action was still undiscovered. Recently, however, a team of researchers were able to uncover the truth behind AHA’s, opening up the potential to use this important cosmetic tool in medical applications.

The research team responsible for the breakthrough was made up of investigators from UC Davis and Peking University and the results of their studies were published in the Journal of Biological Chemistry.The article entitled  “Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes” outlines the basic mechanism of action that accounts for the exfoliation effect of AHA’s on the skin.

AHA’s are derived from natural sources. Sour milk, sugar cane, apples, and citrus fruits all yield AHA’s, which are a group of weak acids that are known for their ability to improve the condition and texture of the skin. AHA’s cause the top layer of skin to flake off, exposing the nicer-looking, fresh skin that lies beneath. The pathway that apparently causes this effect is known is an ion channel known as the transient receptor potential vanilloid 3 (TRPV3), which can be found in the cellular membrane of keratinocytes.

Keratinocytes are the main type of cell found in the outermost epidermal layer of human skin. Of the cells located in the epidermis, 95% of them are keratinocytes. They provide a mostly impermeable membrane that is important in providing us with protection from infection. The ion channel TRPV3 is known for its role in promoting a sensitivity to environmental temperature and normal physiology in the skin.

The scientists performed experiments that involved passing electrical currents across specially prepared cells that were exposed to the AHA’s. By observing the results of these experiments, the investigators were able to develop a model that explains how a substance like glycolic acid could gain entry into keratinocytes in the epidermal layer and generate protons that are free, ultimately cause acidic conditions to develop within the cell. The low pH brought on by the presence of the acids, activates the TRPV3 channel and opens it. This permits calcium ions to pass into the cell which finally leads to the cell’s death when the cell is overloaded with the calcium ions.

Once the cell dies, it is exfoliated which is the whole goal of using AHA’s. Understanding the mechanism of action behind AHA’s can help scientists make better use of them. After all TRPV3 channels are also found in nervous system cells, which will open up new avenues for research into pain control and skin disease.

(Source: plasticsurgerypress.com)

Reinhold Dauskardt, PhD, of Stanford’s Department of Materials Science and Engineering has been studying skin for years. But when he sent his students to look for data on the mechanical properties of skin, they came back empty-handed. A lot was known about skin structure and disease, but few papers actually talked about its mechanical function - its ability to stretch and resist tension without tearing. “That motivated us to get more interested in the skin itself,” said Dauskardt. 

He and his team, including Ph.D. student Krysta Biniek and postdoctoral researcher Kemal Levi, focused on the outmost layer of skin: the stratum corneum. It protects deeper layers from drying out or getting infected, and it’s also our first line of defense against UV radiation. Their study was published in the Proceedings of the National Academy of Sciences (PNAS). 

They found that beyond the well-documented DNA damage and cancer risk, UV rays also change the way the outermost skin cells hold together and respond to strain. 

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Adolescents with acne often avoid seeking medical advice, even when they rate their own acne as severe, a U.S. survey has shown. Most of the 1,214 adolescents surveyed, 57 percent treated their own acne, and only 17 percent had sought medical care. Even among those who rated their acne as severe, most said they had never sought medical treatment for their condition. READ MORE 

Currently, the non-invasive treatment is used by cosmetic clinics as a way to prevent heavy lines and wrinkles from forming on the face.

However, Chicago-based plastic surgeon Anil Shah MD has published a report that shows the solution can also be injected into the skin to lower the amount of sebum it produces – thus reducing the number of clogged pores the patient experiences.

Acne is caused when the skin’s sebaceous glands produce an excessive amount of sebum into the pores. Bacteria then feed on this and reproduce, which causes the pores to become inflamed.

Dr Shah believes the treatment works because the Botox blocks the chemical acetycholine in the dermis of the skin from increasing the amount of sebum produced. It also paralyses the tiny muscles surrounding the skin’s pours that cause them to expand.

“Botox definitely clears up acne,” the doctor stated. “I only treat patients over 20 years old. Their hormonal changes are likely permanent. For them Botox is now the safest, most effective treatment we have.”

See the full story here: http://www.medicaldaily.com/articles/11798/20120829/botox-the-new-way-to-combat-acne.htm

Scientists at The Scripps Research Institute have made a breakthrough in understanding a class of cells that help wounds in skin and other epithelial tissues heal, uncovering a molecular mechanism that pushes the body into wound-repair mode.

The findings, which appear in an advance, online version of the Immunity on August 16, 2012, focus on cells known as γδ (gamma delta) T cells. The new study demonstrates a skin-cell receptor hooks up with a receptor on γδ T-cells to stimulate wound healing.

“This is a major activation pathway for γδ T cells, and it may be a key to treating slow-wound-healing conditions, such as we see in diabetes,” said Scripps Research Professor Wendy L. Havran, senior author of the study. “Chronic non-healing wounds among diabetics and the elderly are an increasing clinical problem.”

Rounding and Multiplying

Havran’s laboratory specializes in the study of γδ T cells, and the team has produced many of the findings in this research field, including the discovery of these cells’ major role in epithelial wound repair. Epithelial tissues are barrier tissues to the outside world, such as skin and the inner surfaces of the gut and lungs.

Normally, γδ T cells reside in these tissues and extend finger-like projections, called dendrites, that contact neighboring epithelial cells. When injury or infection occurs, the epithelial cells signal their damaged condition to the γδ T cells. In response, the T cells retract their dendrites, become round, start proliferating, and secrete growth-factor proteins that stimulate the production of new epithelial cells in the vicinity - thus helping to repair the wound.

Researchers know of very few interactions between epithelial cells and γδ T cells that are involved in this process. Two, however, are known to be crucial. One of these is through the γδ T cell receptor and the other was described in a 2010 Science paper, whose first author was Havran laboratory Senior Staff Scientist Deborah A. Witherden. But these two interactions don’t fully explain the transformation that γδ T cells undergo in the vicinity of wounds. “We’ve wanted to learn more about the molecules that mediate this dramatic change,” Havran said.

Signaling a Transformation

To do that, Witherden identified an antibody that could block keratinocytes’ ability to activate γδ T cells in culture. She found that the antibody bound to a keratinocyte surface receptor called plexin B2. She also found that when lab mice have small skin wounds, their injured keratinocytes express more plexin B2 soon after the wounding occurs - pointing to a role for plexin B2 in signaling skin-cell damage.

The next step was to find plexin B2’s signaling partner on γδ T cells. “Plexin B2 is very similar to other plexin B family members, including plexin B1, which previously has been shown to bind the CD100 receptor on T cells,” said Witherden. “So we thought that perhaps plexin B2 and CD100 can interact as well.”

Further tests revealed that plexin B2 and CD100 do indeed bind tightly together; moreover, γδ T cells can’t go fully into wound-repair mode when they lack CD100. Witherden found as well that skin wounds in mice take an extra day or two to heal when the mice don’t have this receptor. “This is very similar to what we see in mice that lack γδ T cells altogether,” she said.

Removing CD100 from other types of T cells had no effect on wound healing time, indicating that the absence of this receptor specifically on γδ T cells is the reason for the slower healing.

By stimulating CD100 with plexin B2 molecules or even with CD100-binding antibodies, the team showed that this receptor is the principal trigger for the dramatic appendage-retraction and rounding phenomenon seen in γδ T cells after nearby wounds. Without it, the T cells are largely unable to undergo this transformation. “This rounding process seems to be vital for these T cells to function normally in wound healing,” said Witherden.

Potential Clinical Significance

In early follow-on work, the team has found evidence that this same plexin B2-CD100 interaction is also needed for the prompt activation of γδ T cells and wound healing in the lining of mouse intestines-which suggests that this receptor helps govern wound healing in epithelial tissues generally.

The finding clearly is important for the basic scientific understanding of T cells and their functions. But it is likely to have medical significance, too. Non-healing wounds affect more than 4 million people in the United States and are the leading cause of amputations. These chronic wounds have a major impact on patient’s lives and result in enormous health care costs. “If deficiencies in this γδ T cell activation pathway are even partly responsible, then we may be able to develop drugs to boost this pathway and treat conditions involving chronic non-healing wounds,” said Havran.

The γδ T cell population appears to be involved not just in wound healing, but also in defending against other threats to epithelial tissues. “One of the future directions of our research will be to understand the roles of these molecules in T cell activation pathways in fighting infections and tumors,” she added.