@article{1d817eded4124789972c782745e0de3f,
title = "A widening perspective regarding the relationship between anti-epiligrin cicatricial pemphigoid and cancer",
abstract = "Anti-epiligrin cicatricial pemphigoid (AECP) is a chronic, autoimmune, subepidermal blistering disease characterized by circulating anti-basement membrane autoantibodies to laminin 5. Recent studies have shown that patients with this form of cicatricial pemphigoid have an increased relative risk for malignant solid tumors. The mechanism underlying this association of AECP and cancer is unknown, but there is accumulating evidence that laminin 5 plays a central role. In this article we report a patient with AECP and co-associated cutaneous T cell lymphoma and summarize all to date reported cases of AECP associated with malignancies. In addition we provide a review of the biology of laminin 5 and its potential role in cancer development.",
keywords = "Anti-epiligrin cicatricial pemphigoid (AECP), Cancer, Laminin 5",
author = "Elke Sadler and Zelmira Lazarova and Pichaya Sarasombath and Yancey, {Kim B.}",
note = "Funding Information: There is accumulating evidence that laminin 5 expression in cancer cells promotes their growth, invasion, and metastasis [35] . Tumor cells are able to regulate the biological activity of laminin 5 by specific proteolytic processing, performed by matrix metalloproteinases (MMPs) and other matrix proteinases [36] . These enzymes are found to be frequently overexpressed in tumor and surrounding host stromal cells [37] . Several studies have shown that cleavage of laminin 5 chains may downregulate adhesive but upregulate migratory cell activities. An example of the activities described above would include the proteolytic processing of the N-terminal regions of γ2 chains by MMPs that results in enhanced epithelial cell migration but decreased cell adhesion activity [38] . It has been shown that proteolytic processing of the laminin γ2 chain unveils what is referred to as domain III (DIII; or laminin epidermal growth factor-like domain LE), which is able to stimulate cell migration by binding to the epidermal growth factor receptor [39] . Liberation of DIII seems to unveil cryptic biologically active sites that are hidden when DIII is part of the laminin 5 macromolecule. The β3 chain, which is relatively resistant to proteolysis, has also been shown to be partially cleaved at the short arm. This processing event leads to a decrease in cell adhesion activity and the complete loss of the type VII collagen-binding activity of this laminin isoform [22] . Additional evidence that laminin 5 may play a significant role in cancer biology comes from immunohistochemical studies that have shown that laminin 5 or its subunits are highly expressed in various types of human cancers. In particular, the laminin γ2 chain is expressed in tumor cells at the invasion front or in budding tumor cells in many types of human cancers such as adenocarcinomas of the colon, breast, pancreas, and lung, as well as squamous cell carcinomas and melanomas [40–44] . Moreover, it has been demonstrated in adenocarcinomas of the stomach and lung that well-differentiated carcinoma cells often deposit laminin 5 on neoplastic BMs while carcinoma cells invading into the underlying stroma strongly express only the γ2 chain and accumulate it intracellularly [44,45] . Additionally, in vitro studies have demonstrated that proteolytically shed γ2 fragments were not stored in the extracellular matrix, but abundantly detected in the culture fluids [46] . This phenomenon suggests the N-terminal fragments of γ2 chain are incorporated into the circulation and hence may serve as an invasion marker for epithelial carcinomas. Despite the above observations, the biological significance of laminin 5 in invading tumor cells is incompletely understood and somewhat tumor specific as some studies have reported controversial data indicating a reduction or absence of laminin 5 in prostate carcinomas and down-regulation of laminin 5 expression in malignant and metastatic mammary carcinomas [47–50] . Kim B. Yancey is a professor and Chair of the Department of Dermatology at the University of Texas Southwestern Medical Center. He graduated from the University of Georgia (Summa Cum Laude and Valedictorian) and earned his Medical degree (Alpha Omega Alpha) from the Medical College of Georgia (MCG). He performed residency training at MCG and subsequently completed a postdoctoral fellowship in the NIH Dermatology Branch. He is certified by the American Board of Dermatology and holds special competence in dermatologic immunology and diagnostic laboratory immunology. Dr. Yancey is a member of the American Society for Clinical Investigation, the Society for Investigative Dermatology (SID), the American Academy of Dermatology (AAD), and numerous other professional organizations. He is a former director and vice president of the American Board of Dermatology, a current member of the Board of Directors and Executive Committee of the SID, and several editorial boards. He received the AAD's Marion Sulzberger Award in 2007. He has published numerous research manuscripts and monographs, served on an array of grant review panels, and presented invited lectures in the U.S. and abroad. Dr. Yancey has held research support from the National Institutes of Health for over 20 years. ",
year = "2007",
month = jul,
doi = "10.1016/j.jdermsci.2007.02.012",
language = "English (US)",
volume = "47",
pages = "1--7",
journal = "Journal of Dermatological Science",
issn = "0923-1811",
publisher = "Elsevier Ireland Ltd",
number = "1",
}