A Microfluidic Method to Define the Role of Skin Microenvironment in Melanomagenesis
Abstract
The research project proposed here addresses the FY18 PCRP Topic Area Melanoma and other skin cancers and Military Relevance Focus Area Militarily relevant risk factors associated with cancer. The overall goal of this project is to understand how skin cancer melanoma develops from the melanin pigment-producing cells known as melanocytes. Although it is widely accepted that excessive exposure to ultraviolet rays is a risk factor for developing melanoma, the relationship between the sun exposure and the genetic changes that initiate melanoma are not yet fully understood. Additionally, while large areas of skin that contain many (several thousands) melanocytes, only a few (even as low as one) cells end up progressing to become cancer, suggesting that local factors in the skin around melanocytes determine whether a mutated melanocyte eventually produces a melanoma tumor. In this project, we will study how other skin cells, specifically keratinocytes and fibroblasts, and factors secreted by them affect the initial steps in melanoma development. At this time, the proposed research can be considered basic to have immediate clinical application. It will allow us to focus research on factors that contribute to melanoma development. With additional research, the results of the experiments proposed here are expected to identify factors/mechanism that could be targeted for prevention of melanoma. It is expected that it could take between 5 or more years to achieve clinically relevant outcome. As mentioned above, exposure to environmental ultraviolet (UV) radiation is considered a major etiological factor for skin cancer, including malignant melanoma, the deadliest form of skin cancer. Since the ambient UV radiation exposure is greatest during midday hours, the duration of tasks such as long periods of training exercises for soldiers or sailors can influence the daily UV light exposure. Moreover, deployment of military personnel, sometimes with their families and other military beneficiaries, over the past decade in countries with near maximum annual averages of solar radiation potentially increases their risk of skin cancer. In the February 2017 Medical Surveillance Monthly Report, it is documented that during the 15-year period between 2001-2015, rates of malignant melanoma diagnoses among U.S. military members overall increased in an exponential fashion in relation to years of active service. This research has both short- and long-term impact for military health care. In the short-term, our studies will help in understanding the molecular mechanisms by which skin microenvironment contributes to melanoma risk due to UV exposure. This can improve the risk assessment of active duty military personnel for developing melanoma. In the long-term, this research has the potential to open new avenues for prevention and timely treatment of melanoma in its early stages of development and progression. In the research proposed here, we will not be directly studying individuals or biological materials from active duty, military, military families, or Veteran populations. However, the results of this project could allow us to examine and validate them using pre-existing formalin fixed, paraffin embedded normal skin and melanoma tissues from general population. We will also employ a novel and innovative approach to study freshly isolated human skin cells to identify mechanisms responsible for melanoma due to UV exposure.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910478
Entities
People
- Vijayasaradhi Setaluri
Organizations
- United States Army
- University of Wisconsin–Madison