Increased expression of the collagen internalization receptor uPARAP/Endo180 in the stroma of head and neck cancer.
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.
Sulek
Jay
J
Oral & Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Wagenaar-Miller
Rebecca A
RA
Shireman
Jessica
J
Molinolo
Alfredo
A
Madsen
Daniel H
DH
Engelholm
Lars H
LH
Behrendt
Niels
N
Bugge
Thomas H
TH
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D011975:Receptors, Mitogen / Q000096:biosynthesis*
C408294:Endo180; D011975:Receptors, Mitogen