Ann Dermatol.  2013 May;25(2):145-151. 10.5021/ad.2013.25.2.145.

Up-Regulation of Cyclooxygenase 2 and Matrix Metalloproteinases-2 and -9 in Cutaneous Squamous Cell Carcinoma: Active Role of Inflammation and Tissue Remodeling in Carcinogenesis

• Lee JH
• Piao MS
• Choi JY
• Yun SJ
• Lee JB
• Lee SC

• KMID: 2171780
• DOI: http://doi.org/10.5021/ad.2013.25.2.145

Abstract

BACKGROUND
Tissue inflammation and remodeling have been extensively studied in various tumors in relation with their invasiveness and metastasis.
OBJECTIVE
The purpose of this study was to investigate the change in tissue inflammation and remodeling markers in cutaneous squamous cell carcinoma (SCC).
METHODS
Expression levels of cyclooxygenase-2 (COX-2) as an inflammatory marker and matrix metalloproteinases-2 and -9 (MMPs 2/9) as remodeling markers were studied in mouse and human SCCs. Western blot analysis and RT-PCR for COX-2 and MMPs 2/9 were performed with skin samples from SCC patients and chronic ultraviolet B (UVB)-induced SCC from hairless mice.
RESULTS
mRNA and protein levels of COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in mouse SCCs, which were induced by chronic UVB irradiation. Consistently, COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in human SCCs.
CONCLUSION
COX-2 and MMPs 2/9 are up-regulated in well-differentiated cutanous SCC. Our findings indicate that inflammatory and tissue remodeling processes are actively induced during carcinogenesis of cutaneous SCC.

Keyword

Cyclooxygenase 2; MMP-2; MMP-9; SCC

MeSH Terms

Animals
Blotting, Western
Carcinoma, Squamous Cell
Cyclooxygenase 2
Humans
Inflammation
Matrix Metalloproteinases
Mice
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Skin
Up-Regulation
Cyclooxygenase 2
Matrix Metalloproteinases
Prostaglandin-Endoperoxide Synthases
RNA, Messenger

Figure

• 

  Fig. 1 Induction of UVB-induced skin tumors is time-dependent. To induce skin tumors by chronic UVB irradiation, mice were irradiated 3 times per week for up to 32 weeks. At 14 weeks after starting UVB irradiation, skin tumors could be detected on the back of mice; thereafter, the number of skin tumors was counted by unaided gross visual inspection every week. UVB: ultraviolet B.

• 

  Fig. 2 UVB-induced skin tumors are well-differentiated SCCs in mouse. (A) Multiple skin tumors were developed by chronic UVB irradiation on the backs of mice. (B) On a random basis, several tumors were excised with a scalpel, and then paraffin blocks were prepared with H&E staining (×400). UVB: ultraviolet B, SCC: squamous cell carcinoma.

• 

  Fig. 3 COX-2 and MMPs 2/9 are up-regulated in UVB-induced SCC from mouse. (A) Levels of protein expression for COX-2, MMPs 2/9 were determined by Western immunoblots with tissue extracts from UVB-induced SCCs and normal control skin. Control samples are depicted as C1~C6, and tumor samples are depicted as T1~T10. (B) Total RNAs were prepared from UVB-induced SCCs and control skin, and then RT-PCR for COX-2, MMPs 2/9 were performed. Control samples are depicted as C1~C3, and tumor samples are depicted as T1~T3. COX-2: cyclooxygenase-2, MMPs 2/9: matrix metalloproteinases-2 and -9, UVB: ultraviolet B, SCC: squamous cell carcinoma.

• 

  Fig. 4 COX-2 and MMPs 2/9 are up-regulated in cutaneous SCC from human. Expression levels for COX-2 and MMPs 2/9 were determined by Western immunoblots with tissue extracts from cutaneous SCCs (T1~T4) and neighboring normal skin (C1~C4) of the same patient for each sample pair. COX-2: cyclooxygenase-2, MMPs 2/9: matrix metalloproteinases-2 and -9, C: control, T: tumor, SCC: squamous cell carcinoma.

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