Collagen Clinical Study

Sulek J, Wagenaar-Miller RA, Shireman J, Molinolo A, Madsen DH, Engelholm LH, Behrendt N, Bugge TH.

Oral and 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).

Local growth, invasion, and metastasis of malignancies of the head and neck involve extensive degradation and remodeling of the underlying, collagen-rich connective tissue. uPARAP/Endo180 is an endocytic receptor that was recently shown to play a critical role in the uptake and intracellular degradation of collagen by mesenchymal cells. As a step towards 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. The 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, the expression of the collagen internalization receptor was increased in tumor stroma compared to 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.

PMID: 17189524 [PubMed - as supplied by publisher

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