TY - JOUR
T1 - Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α
AU - Xie, Lining
AU - Moroi, Yoichi
AU - Hayashida, Sayaka
AU - Tsuji, Gaku
AU - Takeuchi, Satoshi
AU - Shan, Baoen
AU - Nakahara, Takeshi
AU - Uchi, Hiroshi
AU - Takahara, Masakazu
AU - Furue, Masutaka
N1 - Funding Information:
This work was partly supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the Environment Technology Development Fund of the Ministry of the Environment, Japan.
PY - 2011/1
Y1 - 2011/1
N2 - Background: Cathepsin K (CTSK), a cysteine protease with strong collagenolytic properties, is involved in extracellular matrix turnover. In the previous studies, CTSK expression was detected in peritumoral fibroblasts (Fbs) around squamous cell carcinoma (SCC), but not in those surrounding benign epidermal tumors. However, the mechanism governing CTSK expression in epidermal tumors remains unclear. Objective: To study the regulatory mechanisms of fibroblastic CTSK expression in the SCC-stromal interaction. Methods: We examined dynamic interactions of Fbs with tumorigenic SCC cells (A431 and A253) or normal human keratinocytes. Results: SCC cells and normal keratinocytes did not synthesize CTSK, while Fbs constitutively expressed CTSK. When cocultured, SCC cells upregulated fibroblastic CTSK expression more potently than did normal keratinocytes, which was mainly attributable to SCC-derived IL-1α. Coculturing Fbs with SCC cells significantly augmented the matrigel invasive ability of SCC cells, which was downregulated when cocultured with CTSK knockdown Fbs or in the presence of neutralizing anti-IL-1α antibody. Conclusion: The CTSK-upregulated Fbs generated by SCC-derived IL-1α may play a crucial role in the progression and invasion of SCC.
AB - Background: Cathepsin K (CTSK), a cysteine protease with strong collagenolytic properties, is involved in extracellular matrix turnover. In the previous studies, CTSK expression was detected in peritumoral fibroblasts (Fbs) around squamous cell carcinoma (SCC), but not in those surrounding benign epidermal tumors. However, the mechanism governing CTSK expression in epidermal tumors remains unclear. Objective: To study the regulatory mechanisms of fibroblastic CTSK expression in the SCC-stromal interaction. Methods: We examined dynamic interactions of Fbs with tumorigenic SCC cells (A431 and A253) or normal human keratinocytes. Results: SCC cells and normal keratinocytes did not synthesize CTSK, while Fbs constitutively expressed CTSK. When cocultured, SCC cells upregulated fibroblastic CTSK expression more potently than did normal keratinocytes, which was mainly attributable to SCC-derived IL-1α. Coculturing Fbs with SCC cells significantly augmented the matrigel invasive ability of SCC cells, which was downregulated when cocultured with CTSK knockdown Fbs or in the presence of neutralizing anti-IL-1α antibody. Conclusion: The CTSK-upregulated Fbs generated by SCC-derived IL-1α may play a crucial role in the progression and invasion of SCC.
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U2 - 10.1016/j.jdermsci.2010.09.005
DO - 10.1016/j.jdermsci.2010.09.005
M3 - Article
C2 - 21146373
AN - SCOPUS:78650679889
VL - 61
SP - 45
EP - 50
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 1
ER -