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Originally published as JHC exPRESS on December 22, 2006.
doi:10.1369/jhc.6A7133.2006
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Journal of Histochemistry and Cytochemistry
Volume 55 (4): 347-353, 2007
Copyright ©The Histochemical Society, Inc.

Increased Expression of the Collagen Internalization Receptor uPARAP/Endo180 in the Stroma of Head and Neck Cancer

Jay Sulek, Rebecca A. Wagenaar-Miller, Jessica Shireman, Alfredo Molinolo, Daniel H. Madsen, Lars H. Engelholm, Niels Behrendt and Thomas H. Bugge

Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland (JS,RAW-M,JS,AM,THB), and Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (DHM,LHE,NB)

Correspondence to: Thomas H. Bugge, PhD, Proteases and Tissue Remodeling Unit, Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 211, Bethesda, MD 20892. E-mail: thomas.bugge{at}nih.gov

Local growth, invasion, and metastasis of malignancies of the head and neck involve extensive degradation and remodeling of the underlying, collagen-rich connective tissue. Urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 is an endocytic receptor recently shown to play a critical role in the uptake and intracellular degradation of collagen by mesenchymal cells. As a step toward determining the putative function of uPARAP/Endo180 in head and neck cancer progression, we used immunohistochemistry to determine the expression of this collagen internalization receptor in 112 human squamous cell carcinomas and 19 normal or tumor-adjacent head and neck tissue samples from the tongue, gingiva, cheek, tonsils, palate, floor of mouth, larynx, maxillary sinus, upper jaw, nasopharynx/nasal cavity, and lymph nodes. Specificity of detection was verified by staining of serial sections with two different monoclonal antibodies against two non-overlapping epitopes on uPARAP/Endo180 and by the use of isotype-matched non-immune antibodies. uPARAP/Endo180 expression was observed in stromal fibroblast-like, vimentin-positive cells. Furthermore, expression of the collagen internalization receptor was increased in tumor stroma compared with tumor-adjacent connective tissue or normal submucosal connective tissue and was most prominent in poorly differentiated tumors. These data suggest that uPARAP/Endo180 participates in the connective tissue destruction during head and neck squamous cell carcinoma progression by mediating cellular uptake and lysosomal degradation of collagen. (J Histochem Cytochem 55:347–353, 2007)

Key Words: collagen degradation • Endo180 • head and neck cancer • invasion • squamous cell carcinoma • urokinase plasminogen activator receptor-associated protein


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