Agustin Alejandro Martinez Chibly Abstract
Agustin Alejandro Martinez Chibly
Ph.D. Candidate
Cancer Biology, GIDP
GRC Salivary Glands and Exocrine Biology
Galveston, Texas
February 15-20, 2015
ABSTRACT
Abstract:
Salivary Gland dysfunction is a common consequence of radiotherapy for patients with Head and Neck Cancer, which account for about 50,000 cases per year in the U.S. Dysfunction of the salivary glands presents with the symptom of xerostomia, and may be accompanied by severe mucositis, esophageal dilation, and several other complications that diminish quality of life. Currently, there is no cure for xerostomia or salivary gland dysfunction and the current palliative care fails to improve the quality of life of these patients. Restorative therapies involving salivary gland stem cells are an attractive alternative, but the mechanisms underlying their response to radiation or their role in gland repair remain vastly unknown. Here, we demonstrate that radiation triggers proliferation of salivary progenitors in the acinar compartment of the parotid gland. Further, this proliferative response is ameliorated by administering IGF-1, which has been used in the past to fully regenerate the irradiated salivary glands in mice, suggesting that regulation of proliferation is crucial to achieve restoration of function. Cell polarity has been shown to regulate the function of progenitor cells in several models including drosophila and mammary epithelial cells. Results from this study suggest that activation of a polarity complex (PAR-aPKC) is important for propagation of salivary gland progenitors in vitro, and radiation treatment impairs the activation of the PAR-aPKC polarity complex in salivary gland progenitors in vivo. The importance of this work lies in the potential therapeutic applications of targeting cell polarity to restore function of the irradiated salivary glands.
Abstract (for Lay Audience)
Salivary glands are secretory organs that produce saliva and digestive enzymes distributed throughout the oral cavity. Their main function is to maintain a healthy environment in the mouth by providing saliva, which in turn is comprised mostly of water, electrolytes, proteins that aid in digestion, and antimicrobial enzymes. Salivary glands can be damaged as a side effect of certain kinds of medication, or during the treatment of head and neck cancers with radiotherapy. Radiation therapy affects the salivary glands by causing extensive and irreparable damage to the acinar cells, which are the secretory component of the glands. Some of the complications that arise shortly after or even during radiation treatment include inflammation of the oral mucosa, persistent decrease in saliva production, swelling of the internal membranes of the oral cavity, and many other complications, all of which contribute to a miserable quality of life. Regrettably, there is no cure for salivary gland dysfunction and its associated symptoms, and the existing palliative care is not sufficient to improve the quality of life. Our research focuses on identifying the molecular mechanisms underlying dysfunction of the salivary glands as well as identifying mechanisms of glandular repair. Specifically, we study how progenitor cells can be stimulated to repair damage to the salivary glands. Progenitor cells are a very important cell type that are present in most adult tissues, and their characteristics and function vary depending on the tissue where they reside. In general, it is believed that progenitor cells are responsible for maintaining homeostasis and control in adult tissues by constantly providing new cells to replace for the ones that are lost due to natural cell death. In salivary glands, very limited knowledge is available in regards to the function of salivary gland progenitors, especially in adults. One of our aims is to identify how these progenitors respond to radiation treatment, and whether they play a role in gland repair. This is important because understanding how progenitor cells in salivary glands are affected by radiation damage may provide with important clues for the development of new therapies for salivary gland dysfunction. This has great implications from a public health perspective, since there are about 50,000 cases of head and neck cancer diagnosed every year in the U.S., for which the main treatment is radiotherapy. For most of these patients, salivary gland dysfunction remains an imminent threat that not only would greatly reduce their quality of life, but would also represent a significant economic burden for the rest of their lives. Our research then contributes to the development of new and better therapeutic strategies for salivary gland dysfunction which will greatly improve quality of life.