Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.
Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells.
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Department of Oral Medicine and Pathology, Faculty of Dentistry, Sanaa University, Sanaa, Yemen.
Kamal
K
Al-Eryani
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
Jun
J
Cheng
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan.
Tatsuya
T
Abé
Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan.
Satoshi
S
Maruyama
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
Manabu
M
Yamazaki
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
Hamzah
H
Babkair
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
Ahmed
A
Essa
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan. Electronic address: tsaku@dent.niigata-u.ac.jp.
Takashi
T
Saku
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck
D009842:Oligopeptides; D044464:Receptor, PAR-2; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine
Carcinoma in situ; Cell invasion; Cell proliferation; Oral mucosa; PAR-2; Squamous cell carcinoma