01:54am Thursday 17 August 2017

UCLA study identifies cell of origin for squamous cell cancer

William Lowry William Lowry
The finding could result in new strategies to treat and potentially prevent the disease.
 
Interestingly, the progeny of these cells, although just a few divisions away from the mother hair follicle stem cells, are not capable of forming squamous cell cancers, said the researchers, from UCLA’s Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
 
Further study of why the progeny, known as transit amplifying cells, can’t develop cancer could provide vital clues to how squamous cell cancers originate, said William Lowry, an assistant professor of molecular, cell and developmental biology in the UCLA Life Sciences Division and the senior author of the study.
 
The study, conducted in mouse models, appears the week of April 18 in the early online edition of the peer-reviewed journal Proceedings of National Academy of Sciences.
 
It had been suggested in the scientific literature that squamous cell cancers could arise from the hair follicle, but it was not clear what cell type within the follicle was responsible. The UCLA study represents the first time two distinct cell types in the skin have been compared and contrasted for their ability to develop squamous cell cancers, said Lowry, who is also a scientist at the Jonsson Cancer Center and Broad Stem Cell Research Center.  
 
“It was surprising that the progeny of these stem cells, which are developmentally more restricted, could not develop cancers when the mother stem cells could,” Lowry said. “There is something fundamentally different between the two, and it’s important that we figure out why one type of cell was able to develop cancer and the other was not. The insights we gain will tell us how these cancers arise in the first place and could provide us with a wealth of novel targets we could go after to prevent the cancer before it starts.”
 
A type of non-melanoma skin cancer, these cancers form in squamous cells — thin, flat cells found on the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Squamous cell cancers occur in the skin, lips, mouth, esophagus, bladder, prostate, lungs, vagina, anus and cervix. Despite their common name, these cancers are unique malignancies with significant differences in manifestation and prognosis.
 
In the study, Lowry and his team sought to determine which cells of the epidermis, or skin, could give rise to squamous cell cancer. They wanted to find out if skin stem cells had properties that made them more prone to develop tumors than non-stem cells, said Andrew White, a postdoctoral fellow in Lowry’s lab and the first author of the study.
 
“Adult stem cells are long-lived and can acquire mutations that can cause cancer, but they also have intrinsic properties for self-renewal that are similar to cancer that could make them more tumor-prone,” White said.
 
Lowry and his team delivered genetic hits — adding an oncogene that is known to cause cancer and removing a tumor-suppressor gene — to the hair follicle stem cells and the transit amplifying cells in two groups of mice and waited to see which developed cancer. Only the mice that received the genetic hits in the hair follicle stem cell population developed squamous cell cancer.  
 
Going forward, White will molecularly profile the hair follicle stem cells and the transit amplifying cells to determine what string of biologic events occurs when the cancer-causing genes are delivered. The differences between the two will be illuminating, Lowry said.
 
“We hope that this will lead to much more specific therapies that target cancer initiation rather than treating the disease once it’s established,” Lowry said. “If we’re lucky, a drug may already exist that will hit a target we identify.”
 
The four-year study was funded by the Jonsson Cancer Center Foundation; a training grant from the California Institute for Regenerative Medicine; the National Institutes of Health; the American Cancer Society; the University of California Cancer Research Coordinating Committee; and the Maria Rowena Ross Chair in Cell Biology and Biochemistry.
 
A Belgium-based team also came to similar conclusions using slightly different methods, confirming the UCLA results. That study is published alongside Lowry’s in Proceedings of the National Academy of Sciences.
 
The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA’s stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA’s Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.
 
UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.
 

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