CD10‐bearing fibroblast inhibits matrigel invasive potency of interleukin‐1α‐producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment
CD10‐bearing fibroblast inhibits matrigel invasive potency of interleukin‐1α‐producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment
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DOI：
10.1111/j.1349-7006.2010.01735.x
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发表时间：
2010-12
期刊：
影响因子：
5.7
通讯作者：
Lining Xie;Y. Moroi;G. Tsuji;Min Liu;S. Hayashida;M. Takahara;S. Fukagawa;S. Takeuchi;B. Shan;T. Nakahara;H. Uchi;T. Yokomizo;M. Furue
中科院分区：
文献类型：
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作者：
Lining Xie;Y. Moroi;G. Tsuji;Min Liu;S. Hayashida;M. Takahara;S. Fukagawa;S. Takeuchi;B. Shan;T. Nakahara;H. Uchi;T. Yokomizo;M. Furue
CD 10是一种中性内肽酶，其切割包括P物质在内的各种肽底物。已经在各种癌症如鳞状细胞癌（SCC）的浸润区域内的瘤周成纤维细胞（Fb）中检测到CD 10表达。然而，携带CD 10的Fb的生物学意义在很大程度上仍然未知。我们研究了Fb与致瘤性A431 SCC细胞或非致瘤性HaCaT鳞状细胞的动态相互作用。SCC和HaCaT细胞不合成CD 10，而Fb组成型表达CD 10。当共培养时，与HaCaT相比，SCC显著上调成纤维细胞CD 10表达，这主要归因于SCC源性白细胞介素-1 α（IL-1α）。SCC和Fb均自主分泌P物质，其最终通过上调基质金属蛋白酶（MMP）-1和MMP-2而不是MMP-9来增强SCC在基质胶侵袭试验中的侵袭能力。针对CD 10的siRNA的转染成功地敲低了Fb中的CD 10表达（CD 10 ND-Fb）。在CD 10 ND-Fb的存在下，与对照scramble RNA转染的Fb相比，上清液中的P物质水平以及MMP产生和SCC的侵袭能力显著增强。我们还将CD 10载体转染至Fb，发现与CD 10载体转染的Fb而不是空载体转染的Fb共培养的SCC细胞的基质胶侵袭能力下调。总之，由SCC衍生的IL-1产生的携带CD 10的Fb通过减少P物质的微环境浓度来抑制SCC的侵袭能力（Cancer Sci 2010; 101：2570-2578）。
CD10 is a neutral endopeptidase, which cleaves various peptide substrates including substance P. CD10 expression has been detected in peritumoral fibroblasts (Fb) within the invasive area of various cancers such as squamous cell carcinoma (SCC). However, the biological significance of CD10‐bearing Fb remains largely unknown. We examined dynamic interactions of Fb with tumorigenic A431 SCC cells or non‐tumorigenic HaCaT squamous cells. The SCC and HaCaT cells did not synthesize CD10, while Fb constitutively expressed CD10. When co‐cultured, SCC markedly upregulated fibroblastic CD10 expression compared with HaCaT, which was mainly attributable to SCC‐derived interleukin‐1α (IL‐1α). Both SCC and Fb autonomously secreted substance P, which eventually enhanced the invasive capacity of SCC in a matrigel invasion assay by upregulating matrix metalloproteinase (MMP)‐1 and MMP‐2, but not MMP‐9. Transfection of siRNA for CD10 successfully knocked down the CD10 expression in Fb (CD10ND‐Fb). In the presence of CD10ND‐Fb, substance P levels in supernatants as well as MMP production and the invasive potency of SCC were significantly augmented compared with control scramble RNA‐transfected Fb. We also transfected CD10 vector to Fb and found that the matrigel invasive ability of SCC cells was downregulated co‐cultured with CD10 vector‐transfected Fb rather than empty vector‐transfected Fb. In conclusion, the CD10‐bearing Fb generated by SCC‐derived IL‐1 inhibited the invasive capacity of SCC by diminishing the microenvironmental concentration of substance P. (Cancer Sci 2010; 101: 2570–2578)